Neoplasia de células dendríticas plasmocitoides blásticas. Reporte de un caso / Blastic plasmacytoid dendritic cell neoplasia. Report of a case

RESUMEN La neoplasia de células dendríticas plasmocitoides blásticas (NCDPB) es una malignidad hematológica poco frecuente y generalmente agresiva, por lo cual se requiere su reconocimiento precoz. A continuación, se describe el curso clínico de una paciente de 72 años con NCDPB, en cuyos hallazgos más relevantes destacó la presencia de lesiones cutáneas, organomegalias, infiltración de la médula ósea. Posterior al diagnóstico se indicó quimioterapia sistémica, con buena respuesta, no obstante, a los 2 meses presentó recidiva de lesiones y la paciente falleció. En esta enfermedad es necesario establecer el diagnóstico diferencial con trastornos linfoproliferativos, leucemias linfoides y mieloides agudas, constituyendo el análisis morfológico de las células neoplásicas un aspecto importante para una adecuada orientación diagnóstica.

ABSTRACT Blastic plasmacytoid dendritic cell neoplasia (BCDPN) is a rare and generally aggressive hematological malignancy, which requires early recognition. Below, the clinical course of a 72-year-old patient with NCDPB is described, whose most relevant findings included the presence of skin lesions, organomegaly, and bone marrow infiltration. After the diagnosis, systemic chemotherapy was indicated, with a good response; however, after 2 months the lesions recurred and the patient died. In this disease it is necessary to establish the differential diagnosis with lymphoproliferative disorders, lymphoid and acute myeloid leukemias, with the morphological analysis of the neoplastic cells being an important aspect for adequate diagnostic guidance.

Sarcoma folicular de células dendríticas mediastinal: primer reporte de caso en Costa Rica / Mediastinal Follicular Dendritic Cell Sarcoma: First Case Report in Costa Rica

El sarcoma folicular de células dendríticas (SFCD) es una neoplasia maligna rara derivada de las células dendríticas foliculares. Ha sido clasificado, dadas sus características inmunohistoquímicas, como parte del grupo de los sarcomas, donde representa un porcentaje menor al 1%. Actualmente, existen menos de 1.000 reportes en la literatura a nivel mundial, lo cual plantea una dificultad no sólo diagnóstica, siendo confundido frecuentemente con neoplasias de tipo linfoide; sino también terapéutica al no existir un claro consenso sobre su manejo definitivo. Esta revisión de caso clínico describe el primer caso reportado de SFCD en Costa Rica.

Follicular dendritic cell sarcoma (SFCD) is a rare malignant neoplasm derived from follicular dendritic cells, which has been classified, given its immunohistochemical characteristics, as part of the group of sarcomas, where it represents less than 1%. Currently, there are less than 1000 reports in the literature worldwide, which generates a difficulty not only in diagnosis, being frequently confused with lymphoid type neoplasms; but also, as therapeutic as there is no clear consensus on its definitive management. This clinical case review describes the first reported case of SFCD in Costa Rica.

Estudo da ativação e modulação da resposta imune contra a esporotricose experimental, a partir de vesículas extracelulares purificadas de células dendríticas / Study of the activation and modulation of the immune response against experimental sporotrichosis, using extracellular vesicles purified from dendritic cells

A esporotricose é uma zoonose micótica emergente e subcutânea, que afeta a pele, o sistema linfático e outros órgãos de humanos e animais. Assim como outras doenças infecciosas fúngicas, se torna ainda mais grave quando acomete pacientes imunossuprimidos. Essa infecção possui distribuição global e é endêmica em algumas regiões do Brasil e de outros países tropicais e subtropicais, sendo um problema de saúde pública importante em nosso país. A doença é causada por um complexo de pelo menos quatro espécies patogênicas, incluindo o Sporothrix brasiliensis (S. brasiliensis). A resposta imunológica contra estas espécies ainda não é completamente elucidada, mas estruturas como as vesículas extracelulares (VEs) poderiam transportar componentes importantes que podem contribuir na modulação e no controle desta importante infecção. Assim, o objetivo deste trabalho, é analisar a participação das VEs de células dendríticas (DCs) naive e VEs de DCs previamente primadas com leveduras de S. brasiliensis e primadas com VEs do fungo, na resposta imune contra a esporotricose experimental em modelos murinos. Para isso, as DCs obtidas da medula óssea de camundongos, foram cultivadas com leveduras de S. brasiliensis ou com VEs do fungo e posteriormente, VEs totais das DCs foram purificadas a partir de ultracentrifugação e analisadas quanto a sua participação na modulação da resposta imunológica. Essas VEs foram utilizadas em protocolo profilático em modelos murinos, previamente a infecção subcutânea experimental. Foi observado o diâmetro médio das lesões no decorrer de 35 dias de infecção e a carga fúngica da lesão na pele. Os resultados obtidos mostram que as VEs de DCs naive, e VEs de DCs previamente cultivadas com leveduras do fungo ou com VEs fúngicas, são capazes de modular a carga fúngica. Os grupos que receberam VEs de DCs de forma profilática, de modo geral apresentaram diminuição significativa da carga fúngica em relação ao grupo controle. Na análise comparativa apenas dos grupos que receberam a profilaxia, observa-se que o uso de VEs de DCs naive, resultam em uma carga fúngica maior que o uso de VEs de DCs previamente ativadas, e quando as DCs são ativadas com levedura, essa carga fúngica é a menor. Quando analisamos o perfil de citocinas na pele de camundongos tratados com as VEs previamente a infecção, observamos aumento de IFN-γ, TNF-α, IL-17 e IL-10 principalmente nos animais previamente tratados com VEs de DCs que foram ativadas com leveduras. Em relação às citocinas produzidas, podemos sugerir até o momento, uma resposta imunológica mista, mas que de alguma maneira, ainda não esclarecida, devem contribuir para melhor controle do processo infeccioso in vivo. Em relação a linfoproliferação, observa-se principalmente um aumento de linfócitos T CD4+ quando acrescentamos VEs de DCs que não foram previamente ativadas, mostrando uma ação de uma resposta mais inespecífica. Vale ressaltar que todos os protocolos profiláticos foram capazes de modular e minimizar o crescimento fúngico, quando comparados ao controle, ou seja, as VEs contribuíram com o controle da infecção e agiram a favor do hospedeiro, demonstrando um caráter protetivo

Sporotrichosis is an emerging subcutaneous mycotic zoonosis that affects the skin, lymphatic system, and other organs of humans and animals, and like other infectious fungal diseases, it becomes even more serious when it affects immunosuppressed patients. This infection has a global distribution and is endemic in some regions of Brazil and other tropicals and subtropicals countries, being an important public health problem in our country. The disease is caused by a complex of at least four pathogenic species, including Sporothrix brasiliensis (S. brasiliensis). The immunological response against these species has not yet been completely elucidated, but structures such as extracellular vesicles (EVs) could carry important components that can contribute to the modulation and control of this important infection. Thus, the objective of this work is to analyze the participation of EVs from naïve dendritic cells (DCs) and EVs from DCs previously primed with S. brasiliensis yeast and primed with EVs from the fungus, in the immune response against experimental sporotrichosis in murine models. For this, DCs obtained from the bone marrow of mice were cultivated with S. brasiliensis yeast or EVs from the fungus, and subsequently, total EVs from the DCs were purified through ultracentrifugation and analyzed for their participation in modulating the immune response. These EVs were used in a prophylactic protocol in murine models, before experimental subcutaneous infection. The average diameter of the lesions over 35 days of infection and the fungal load of the lesion on the skin were observed. The results obtained show that EVs from naïve DCs, and EVs from DCs previously cultured with yeast or fungal EVs, are capable of modulating the fungal load. The groups that received EVs from DCs prophylactically generally showed a significant decrease in fungal load compared to the control group. In the comparative analysis of only the groups that received prophylaxis, it was observed that the use of EVs from naïve DCs results in a higher fungal load than the use of EVs from previously activated DCs, and when the DCs are activated with yeast, this load fungal is smaller. When we analyzed the cytokine profile in the skin of mice treated with EVs before infection, we observed an increase in IFN-γ, TNF-α, IL-17, and IL-10, mainly in animals previously treated with EVs from DCs that were activated with yeast. About the cytokines produced, we can so far suggest a mixed immunological response, but in some way, not yet clear, they should contribute to better control of the infectious process in vivo. About lymphoproliferation, an increase in CD4+ T lymphocytes is mainly observed when we add EVs from DCs that were not previously activated, showing a more nonspecific response. It is worth highlighting that all prophylactic protocols were able to modulate and minimize fungal growth, when compared to the control, that is, EVs contributed to the control of the infection and acted in favor of the host, demonstrating a protective character

Estudo da ativação e modulação da resposta imune contra a esporotricose experimental, a partir de vesículas extracelulares purificadas de células dendríticas / Study of the activation and modulation of the immune response against experimental sporotrichosis, using extracellular vesicles purified from dendritic cells

A esporotricose é uma zoonose micótica emergente e subcutânea, que afeta a pele, o sistema linfático e outros órgãos de humanos e animais. Assim como outras doenças infecciosas fúngicas, se torna ainda mais grave quando acomete pacientes imunossuprimidos. Essa infecção possui distribuição global e é endêmica em algumas regiões do Brasil e de outros países tropicais e subtropicais, sendo um problema de saúde pública importante em nosso país. A doença é causada por um complexo de pelo menos quatro espécies patogênicas, incluindo o Sporothrix brasiliensis (S. brasiliensis). A resposta imunológica contra estas espécies ainda não é completamente elucidada, mas estruturas como as vesículas extracelulares (VEs) poderiam transportar componentes importantes que podem contribuir na modulação e no controle desta importante infecção. Assim, o objetivo deste trabalho, é analisar a participação das VEs de células dendríticas (DCs) naive e VEs de DCs previamente primadas com leveduras de S. brasiliensis e primadas com VEs do fungo, na resposta imune contra a esporotricose experimental em modelos murinos. Para isso, as DCs obtidas da medula óssea de camundongos, foram cultivadas com leveduras de S. brasiliensis ou com VEs do fungo e posteriormente, VEs totais das DCs foram purificadas a partir de ultracentrifugação e analisadas quanto a sua participação na modulação da resposta imunológica. Essas VEs foram utilizadas em protocolo profilático em modelos murinos, previamente a infecção subcutânea experimental. Foi observado o diâmetro médio das lesões no decorrer de 35 dias de infecção e a carga fúngica da lesão na pele. Os resultados obtidos mostram que as VEs de DCs naive, e VEs de DCs previamente cultivadas com leveduras do fungo ou com VEs fúngicas, são capazes de modular a carga fúngica. Os grupos que receberam VEs de DCs de forma profilática, de modo geral apresentaram diminuição significativa da carga fúngica em relação ao grupo controle. Na análise comparativa apenas dos grupos que receberam a profilaxia, observa-se que o uso de VEs de DCs naive, resultam em uma carga fúngica maior que o uso de VEs de DCs previamente ativadas, e quando as DCs são ativadas com levedura, essa carga fúngica é a menor. Quando analisamos o perfil de citocinas na pele de camundongos tratados com as VEs previamente a infecção, observamos aumento de IFN-γ, TNF-α, IL-17 e IL-10 principalmente nos animais previamente tratados com VEs de DCs que foram ativadas com leveduras. Em relação às citocinas produzidas, podemos sugerir até o momento, uma resposta imunológica mista, mas que de alguma maneira, ainda não esclarecida, devem contribuir para melhor controle do processo infeccioso in vivo. Em relação a linfoproliferação, observa-se principalmente um aumento de linfócitos T CD4+ quando acrescentamos VEs de DCs que não foram previamente ativadas, mostrando uma ação de uma resposta mais inespecífica. Vale ressaltar que todos os protocolos profiláticos foram capazes de modular e minimizar o crescimento fúngico, quando comparados ao controle, ou seja, as VEs contribuíram com o controle da infecção e agiram a favor do hospedeiro, demonstrando um caráter protetivo

Sporotrichosis is an emerging subcutaneous mycotic zoonosis that affects the skin, lymphatic system, and other organs of humans and animals, and like other infectious fungal diseases, it becomes even more serious when it affects immunosuppressed patients. This infection has a global distribution and is endemic in some regions of Brazil and other tropicals and subtropicals countries, being an important public health problem in our country. The disease is caused by a complex of at least four pathogenic species, including Sporothrix brasiliensis (S. brasiliensis). The immunological response against these species has not yet been completely elucidated, but structures such as extracellular vesicles (EVs) could carry important components that can contribute to the modulation and control of this important infection. Thus, the objective of this work is to analyze the participation of EVs from naïve dendritic cells (DCs) and EVs from DCs previously primed with S. brasiliensis yeast and primed with EVs from the fungus, in the immune response against experimental sporotrichosis in murine models. For this, DCs obtained from the bone marrow of mice were cultivated with S. brasiliensis yeast or EVs from the fungus, and subsequently, total EVs from the DCs were purified through ultracentrifugation and analyzed for their participation in modulating the immune response. These EVs were used in a prophylactic protocol in murine models, before experimental subcutaneous infection. The average diameter of the lesions over 35 days of infection and the fungal load of the lesion on the skin were observed. The results obtained show that EVs from naïve DCs, and EVs from DCs previously cultured with yeast or fungal EVs, are capable of modulating the fungal load. The groups that received EVs from DCs prophylactically generally showed a significant decrease in fungal load compared to the control group. In the comparative analysis of only the groups that received prophylaxis, it was observed that the use of EVs from naïve DCs results in a higher fungal load than the use of EVs from previously activated DCs, and when the DCs are activated with yeast, this load fungal is smaller. When we analyzed the cytokine profile in the skin of mice treated with EVs before infection, we observed an increase in IFN-γ, TNF-α, IL-17, and IL-10, mainly in animals previously treated with EVs from DCs that were activated with yeast. About the cytokines produced, we can so far suggest a mixed immunological response, but in some way, not yet clear, they should contribute to better control of the infectious process in vivo. About lymphoproliferation, an increase in CD4+ T lymphocytes is mainly observed when we add EVs from DCs that were not previously activated, showing a more nonspecific response. It is worth highlighting that all prophylactic protocols were able to modulate and minimize fungal growth, when compared to the control, that is, EVs contributed to the control of the infection and acted in favor of the host, demonstrating a protective character

Diacerein mitigates renal ischemia/reperfusion injury via inhibition of renal inflammation, dendritic cells maturation and apoptosis: the role of TLR4/NF-kB/NLRP3/IL-1beta signaling pathway / La diacereína mitiga la lesión por isquemia/reperfusión renal a través de la inhibición de la inflamación renal, la maduración de las células dendríticas y la apoptosis: el papel de la vía de señalización TLR4/NF-kB/NLRP3/IL-1beta

SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.

La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.

Mecanismo de células dendríticas derivadas de sangre periférica humana en la regulación de la autofagia en células de carcinoma / Mechanism of human peripheral blood-derived dendritic cells in the regulation of autophagy in carcinoma cells

Resumen Introducción: Las células dendríticas (CD) están involucradas en el reconocimiento, respuesta y modulación inmunológicos relacionados con la aparición del cáncer. Objetivo: Explorar el mecanismo de las CD en la inhibición de la autofagia de las células del hepatoma. Métodos: Células mononucleares de sangre periférica humana se aislaron mediante centrifugación en gradiente de densidad de Ficoll y se indujeron en CD, las cuales fueron cocultivadas con células HepG2 por ensayo de migración Transwell. La actividad de las células HepG2 se determinó mediante ensayo CCK8. La expresión del índice de autofagia LC3 se midió con análisis de transferencia Western y la expresión y secreción de citocinas mediante qRT-PCR y ELISA. Resultados: En el sistema de cocultivo, las CD redujeron la viabilidad de HepG2; la expresión de IL-2, IL-12, IL-10 e IFN-γ en CD también se inhibió significativamente, si bien IL-2 e IFN-γ aún se expresaron 0.6 y 0.53 más que en el grupo de control. Conclusión: Las CD pueden regular la autofagia de las células del carcinoma hepatocelular. El mecanismo puede estar relacionado con la síntesis y liberación de citocinas como IL-2, IL-12 e IFN-γ por parte de las CD.

Abstract Introduction: Dendritic cells (DC) are involved in immune recognition, response and immunomodulation mechanisms related to the onset of cancer. Objective: To explore DCs mechanism in the inhibition of autophagy in hepatoma cells. Methods: Human peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and induced into DCs, which were co-cultured with HepG2 cells by Transwell migration assay. HepG2 cell activity was determined using the CCK8 assay. LC3 autophagy index expression was measured with Western blot analysis, and the expression and secretion of cytokines, with qRT-PCR and ELISA. Results: In the co-culture system, DCs were able to reduce HepG2 cells viability; IL-2, IL-12, IL-10 and IFN-γ expression in DCs was also significantly inhibited, although IL-2 and IFN-γ were still expressed 0.6 and 0.53 more than in the control group. Conclusion: DCs can regulate autophagy in hepatocellular carcinoma cells. The mechanism may be related to the synthesis and release of cytokines such as IL-2, IL-12 and IFN-γ by DCs.

Novas perspectivas em imunoterapia: a importância das células dendríticas na imunoterapia alérgeno-específica / New perspectives in immunotherapy: the importance of dendritic cells in allergen-specific immunotherapy

A imunoterapia alérgeno-específica é o único tratamento capaz de alterar o curso natural da doença alérgica. Ensaios clínicos mostram que a imunoterapia é segura e eficaz para muitos pacientes. No entanto, ainda enfrenta problemas relacionados à eficácia, segurança, longa duração do tratamento e baixa adesão dos pacientes. Neste contexto, tem havido intensa pesquisa no desenvolvimento de adjuvantes com objetivo de aumentar a segurança, otimizar os esquemas de tratamento e melhorar a adesão dos pacientes. Alérgenos foram modificados (glicoconjugados) com carboidratos derivados de Saccharomyces cerevisae para aumentar sua captação e apresentação através dos receptores de carboidratos presentes nas células dendríticas, beneficiando-se da capacidade de atuarem na indução de tolerância para iniciar respostas imunes. À luz de novas evidências, essas células constituem alvo terapêutico chave para se obter uma resposta adequada à imunoterapia alérgeno-específica, com potencial de contribuição na inovação do campo da Imunoterapia.

Allergen-specific immunotherapy is the only treatment capable of altering the natural course of allergic disease. Clinical trials have shown that immunotherapy is safe and effective for many patients. However, it still faces problems related to efficacy, safety, long treatment duration and poor patient compliance. In this context, there has been intense research into the development of adjuvant treatments that increase safety, optimize treatment regimens, and improve patient compliance. Allergens were modified (glycoconjugated) with carbohydrates derived from Saccharomyces cerevisae to increase their uptake and presentation through carbohydrate receptors in dendritic cells, benefiting from their ability to induce tolerance and initiate immune response. In light of the new evidence, these cells are a key therapeutic target for adequate response to allergenspecific immunotherapy and can drive innovation in the field of immunotherapy.

Mechanism of human peripheral blood-derived dendritic cells in the regulation of autophagy in carcinoma cells.

INTRODUCTION: Dendritic cells (DC) are involved in immune recognition, response and immunomodulation mechanisms related to the onset of cancer. OBJECTIVE: To explore DCs mechanism in the inhibition of autophagy in hepatoma cells. METHODS: Human peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and induced into DCs, which were co-cultured with HepG2 cells by Transwell migration assay. HepG2 cell activity was determined using the CCK8 assay. LC3 autophagy index expression was measured with Western blot analysis, and the expression and secretion of cytokines, with qRT-PCR and ELISA. RESULTS: In the co-culture system, DCs were able to reduce HepG2 cells viability; IL-2, IL-12, IL-10 and IFN-γ expression in DCs was also significantly inhibited, although IL-2 and IFN-γ were still expressed 0.6 and 0.53 more than in the control group. CONCLUSION: DCs can regulate autophagy in hepatocellular carcinoma cells. The mechanism may be related to the synthesis and release of cytokines such as IL-2, IL-12 and IFN-γ by DCs.

INTRODUCCIÓN: Las células dendríticas (CD) están involucradas en el reconocimiento, respuesta y modulación inmunológicos relacionados con la aparición del cáncer. OBJETIVO: Explorar el mecanismo de las CD en la inhibición de la autofagia de las células del hepatoma. MÉTODOS: Células mononucleares de sangre periférica humana se aislaron mediante centrifugación en gradiente de densidad de Ficoll y se indujeron en CD, las cuales fueron cocultivadas con células HepG2 por ensayo de migración Transwell. La actividad de las células HepG2 se determinó mediante ensayo CCK8. La expresión del índice de autofagia LC3 se midió con análisis de transferencia Western y la expresión y secreción de citocinas mediante qRT-PCR y ELISA. RESULTADOS: En el sistema de cocultivo, las CD redujeron la viabilidad de HepG2; la expresión de IL-2, IL-12, IL-10 e IFN-γ en CD también se inhibió significativamente, si bien IL-2 e IFN-γ aún se expresaron 0.6 y 0.53 más que en el grupo de control. CONCLUSIÓN: Las CD pueden regular la autofagia de las células del carcinoma hepatocelular. El mecanismo puede estar relacionado con la síntesis y liberación de citocinas como IL-2, IL-12 e IFN-γ por parte de las CD.

Sarcoma de células dendríticas foliculares. Informe de un caso.

ANTECEDENTES: El sarcoma de células dendríticas foliculares es una enfermedad rara, caracterizada principalmente en sitios nodales como la cabeza, el cuello y la orofaringe, aunque puede ser extranodal, como en el bazo y el hígado. En la mayoría de los casos cursa asintomática, pero puede presentar síntomas generales, dolor abdominal o fiebre. La inmunohistoquímica es indispensable para llegar a un diagnóstico definitivo. PRESENTACIÓN DEL CASO: Mujer de 40 años, con abultamiento submaxilar en el cuello, región frontoparietooccipital derecha, y sequedad de mucosa oral. Se manejó inicialmente como un síndrome de Sjögren, que fue descartado por el resultado histopatológico de la biopsia de glándula salival. Posteriormente se realizó biopsia de ganglio del cuello, que reportó sarcoma de células dendríticas foliculares con expresión inmunohistoquímica positiva para CD23 y negativa para CD21 y ACL. Se manejó con samario y tuvo una sobrevida de 3 meses desde el diagnóstico. CONCLUSIONES: el sarcoma de células dendríticas foliculares es raro y la sobrevida es corta. BACKGROUND: Follicular dendritic cell sarcoma is a rare pathology, it occurs mainly in nodal sites such as head, neck, oropharynx, although extranodal presentation such as spleen and liver may occur. In most cases it is asymptomatic but may present general symptoms, abdominal pain or fever. Immunohistochemistry is essential to make a definitive diagnosis. CASE PRESENTATION: Forty year-old woman, with submaxillary lesion, in the neck, right fronto-parieto-occipital region with dry oral mucosa. It was initially managed as a Sjögren's syndrome ruled out by the histopathological result of salivary gland biopsy. Subsequently, a neck ganglion biopsy was performed that reported follicular dendritic cell sarcoma, with positive immunohistochemical expression for CD23 and negative for CD21 and LCA. It was managed with samarium with a survival of 3 months from the time of its diagnosis. CONCLUSIONS: Follicular dendritic cell sarcoma is rare and its global survival is short.

Estudo da dinâmica celular da pele após tratamento epicutâneo com 7,12- Dimetilbenzantraceno em modelo murino de inflamação aguda / Study of skin cellular dynamic under 7,12 dimethylbenzantracene (DMBA) treatment in murine model of acute inflammatory response: the role of Ahr gene

The skin immune system is composed of different cell types of the innate immunity, among them the classic dendritic cells, Langerhans cells and Tγδ lymphocytes that are part of a set of cells which play a fundamental role in protecting against external infectious agents or carcinogenesis control. Found mainly in the epidermis, these cells constitute the cellular group of skin immunity and, therefore, are important for the study of cutaneous carcinogenesis. Polycyclic aromatic hydrocarbons (PAH) such as 7,12-dimethylbenzanthracene (DMBA), a synthetic prototype, present toxic action when coming in contact with skin. DMBA binds to the Aryl hydrocarbon receptor (AHR) in the cytoplasm to act as a Transcription Factor within the nucleus by inducing different genes transcription, including CYPs enzymes (P450) important in the PAH metabolism. Here, we analyzed the tumorigenic action of DMBA when applied on the skin of phenotypically selected mice for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response. These mice, due the AHR genetic polymorphism, the DMBA action on the skin induces papillomas appearance and a particular cell dynamic in each lines of mice. Thus, we treated groups of 6 mice of each group, Acetone (control), and DMBA (5 consecutive applications). A second approach was carried out with the association of TPA (12-O-tetradecanoylphorbol- 13-acetate) and DMBA. In both approaches we evaluated the number of cutaneous lesions, skin histology and cell populations in the epidermis and dermis. We found that, for the two protocols used, AIRmin mice showed greater sensitivity to DMBA concerning the multiplicity and incidence of papillomas, the skin architecture and the presence of two Tγδ lymphocyte populations and dendritic cells. These characteristics observed mainly in AIRmin mice depend on their particular sensitivity to DMBA and open a field to identify the cellular mechanisms operating in the sensitivity to HPA carcinogens. Studies focusing on the two populations of Tγδ lymphocytes and dendritic cells may be promising in the sense of the therapeutic studies aiming to control the non-melanoma skin carcinogenesis development.

O sistema imunológico da pele é composto por diversas células que compõem a imunidade inata, dentre elas destacam-se as células dendríticas clássicas, de Langerhans e linfócitos Tγδ que fazem parte de um conjunto de células que possuem um papel fundamental na proteção contra agentes externos infecciosos e com funções importantes na carcinogênese. Localizadas principalmente na epiderme, essas células constituem o grupo celular da imunidade inata de proteção da pele e, por isso, são importantes para o estudo de carcinogênese cutânea. Tratando-se de agentes cancerígenos, podem-se destacar os hidrocarbonetos policíclicos aromáticos como, por exemplo, o 7,2-dimethylbenzanthraceno (DMBA) um protótipo sintético que possui ação tóxica quando em contato com a pele. O DMBA liga-se ao receptor Aril hidrocarboneto (AHR) localizado no citoplasma das células para exercer suas funções de Fator de Transcrição, induzindo a transcrição de diferentes genes, incluindo as enzimas CYPs importantes na metabolização dos compostos HPA. No presente estudo, analisamos a ação tumorigênica do DMBA quando aplicado na pele de camundongos fenotipicamente selecionados para resposta inflamatória aguda máxima (AIRmax) ou mínima (AIRmin). Esses animais, por apresentarem polimorfismo genético no gene codificador do AHR, a ação do DMBA na pele induz o aparecimento de papilomas em número diferente e provavelmente propicia uma dinâmica celular particular em cada uma dessas linhagens. Assim, tratamos grupos de 6 animais de cada linhagem com Acetona (controle), DMBA (cinco aplicações) e avaliamos o aparecimento de lesões durante 62 dias. Um segundo protocolo com a associação de TPA (12-O- Tetradecanoylphorbol-13-acetate) e DMBA foi realizado com 3 animais de cada grupo e avaliados aos 78 dias após os tratamentos. Em ambos os experimentos avaliamos as características histopatológicas e a presença de populações celulares na epiderme e derme. Verificamos que, para os dois protocolos utilizados, os animais AIRmin apresentaram maior sensibilidade ao DMBA quando avaliamos a multiplicidade e a incidência de papilomas, as estruturas internas da pele e a presença principalmente de duas populações de linfócitos Tγδ e populações de células dendríticas. Essas características observadas nos camundongos AIRmin refletem sua maior sensibilidade ao DMBA e abre campo de estudo para identificar mecanismos celulares operantes na sensibilidade a carcinógenos do tipo HPA. Estudos focando as duas populações de linfócitos Tγδ e as populações de células dendríticas pode ser promissor no sentido de indicar essas células como alvos terapêuticos para o controle da carcinogênese de pele não melanoma.

Ausencia de expresión de la proteína Core del virus de la hepatitis C en células dendríticas derivadas de monocitos humanos utilizando virus del Bosque de Semliki recombinante / Lack of expression of hepatitis c virus core protein in human monocyte-derived dendritic cells using recombinant semliki forest virus

ABSTRACT Hepatitis C Virus belongs to the Flaviviridae family. One proposed mechanism of HCV persistence in the ability to infect hematopoietic cells, including Dendritic cells (DCs). HCV infection of DCs could impair their functions that represent one of the mechanisms, thus hampering viral clearance by the host immune system. Among HCV-encoded proteins, the highly conserved Core protein has been suggested to be responsible for the immunomodulatory properties of this Hepacivirus. Recombinant viral vectors expressing the HCV Core protein and allowing its transduction and therefore the expression of the protein into DCs could be useful tools for the analysis of the properties of the Core protein. Vaccinia Virus and retrovirus have been used to transduce human DCs. Likewise, gene transfer into DCs using Semliki Forest Virus has been reported. This study aimed to express the HCV Core protein in human monocyte-derived DCs using an SFV vector, in which the subgenomic RNA encoding the structural proteins was replaced by the HCV Core sequence and then analyze the effects of its expression on DCs functions.

RESUMEN El virus de la Hepatitis C (VHC) pertenece a la familia Flaviviridae. Uno de los mecanismos propuestos de la persistencia del VHC es la capacidad de infectar células hematopoyéticas, incluidas las células dendríticas (DCs). La infección por VHC de DCs podría alterar sus funciones y corresponde a uno de los mecanismos que impiden el aclaramiento de la infección por VHC por el sistema inmunitario del hospedero. Entre las proteínas codificadas por el VHC, se ha sugerido que la proteína Core, altamente conservada, es responsable de las propiedades inmunomoduladoras de este Hepacivirus. Los vectores virales recombinantes que expresan la proteína Core y permiten su transducción a DCs podrían ser herramientas útiles para el análisis de las propiedades de esta proteína. El virus Vaccinia y el retrovirus se han utilizado para la transducción de DCs humanas. Del mismo modo, la transducción de DCs usando el virus del bosque de Semliki ha sido reportada. El objetivo de este estudio fue expresar la proteína Core de VHC en DCs derivadas de monocitos humanos utilizando un vector de SFV, en el que el ARN subgenómico que codifica las proteínas estructurales fue reemplazado por la secuencia Core del VHC y evaluar los efectos de su expresión en las funciones de DCs.

Las células dendríticas plasmacitoides evocan la respuesta efectora de los linfocitos T citotóxicos específicos para Salmonella / The plasmacytoid dendritic cells evoke Salmonella-specific CTL effector response

Resumen Introducción. La función inmunológica de las células dendríticas plasmacitoides durante las infecciones bacterianas, como la de Salmonella spp., es poco conocida. En ese contexto, se analizó su función efectora para presentar antígenos de Salmonella Typhimurium ante linfocitos T citotóxicos. Objetivo. Analizar la respuesta de los linfocitos T citotóxicos específicos para Salmonella evocada por las células dendríticas plasmacitoides. Materiales y métodos. Se usaron células dendríticas plasmacitoides marcadas con éster de succinimidil-carboxifluoresceína, pulsadas con el epítopo de Salmonella OmpC73 Kb- restringido o infectadas con S. Typhimurium como blanco en ensayos de citotoxicidad. Resultados. La lisis específica tuvo significación estadística usando células dendríticas plasmacitoides positivas pulsadas con OmpC73 en todas las relaciones de células efectoras y blanco (E:B) (p≤0,05); en cuanto a las células dendríticas plasmacitoides positivas para S. Typhimurium, solo se observó significación estadística en la relación de 1:100 (p≤0,05) usando las células efectoras OmpC73. Conclusión. Las células dendríticas plasmacitoides pueden evocar la respuesta de los linfocitos T citotóxicos durante la infección con S. Typhimurium.

Abstract Introduction: The immunological role of plasmacytoid dendritic cells (pDC) in bacterial infections such as Salmonella has been poorly documented. Therefore, we analyzed the effector function of these cells by presenting cytotoxic T lymphocytes (CTL) with Salmonella Typhimurium antigens. Objective: To analyze the Salmonella-specific CTL response evoked by pDCs. Materials and methods: We used plasmacytoid dendritic cells stained with carboxyfluorescein succinimidyl ester (CFSE) and pulsed with OmpC73, Salmonella Kb- restricted epitopes or S. Typhimurium as targets for cytotoxicity assays. Results: Specific lysis was shown to be statistically significant in pDC + OmpC73 for all effector:target ratios (p≤0.05). For pDC + S. Typhimurium, statistical significance was only observed at a 1:100 ratio (p≤0.05) using OmpC73. Conclusion: Plasmacytoid dendritic cells evoke CTL response during S. Typhimurium infection.

Neoplasia blástica de células dendríticas plasmocitoides variante leucemia aguda: reporte de un caso / Blastic plasmacytoid dendritic cell neoplasm variant acute leukemia: case report

RESUMEN La neoplasia blástica de células dendríticas plasmocitoides (NBCDP) es una malignidad hematológica poco frecuente y generalmente agresiva, por lo cual se requiere su reconocimiento precoz. A continuación, se describe el curso clínico prolongado de un paciente masculino de 60 años con NBCDP procedente de Venezuela, en cuyos hallazgos más relevantes destacó la presencia de lesiones cutáneas, organomegalias, infiltración de la médula ósea y del sistema nervioso central. Posterior al diagnóstico se indicó quimioterapia sistémica, no obstante, el paciente falleció por complicaciones respiratorias durante la fase de inducción del tratamiento. En esta enfermedad es necesario establecer el diagnóstico diferencial con trastornos linfoproliferativos, leucemias linfoides y mieloides agudas, constituyendo el análisis morfológico de las células neoplásicas un aspecto importante para una adecuada orientación diagnóstica.

ABSTRACT Blastic plasmacytoid dendritic cell blast neoplasm (BPDCN) is a rare and generally aggressive hematologic malignancy, requiring early recognition. Below is a description of the prolonged clinical course of a 60-year-old male patient with BPDCN from Venezuela, whose most relevant findings highlighted the presence of skin lesions, organomegaly, infiltration of the bone marrow and central nervous system. Systemic chemotherapy was prescribed after diagnosis; however, the patient died of respiratory complications during the induction phase of treatment. In this disease, it is necessary to establish the differential diagnosis with lymphoproliferative disorders, acute lymphoid and myeloid leukemias. The morphological analysis of neoplastic cells is, thus, an important aspect toward proper diagnostic guidance.

Sarcoma de células dendríticas foliculares: una entidad poco frecuente / Follicular dendritic cell sarcoma: an unsual entity

Los sarcomas de células dendríticas foliculares son neoplasias linfoides extremadamente raras. Afectan primordialmente a ganglios linfáticos con compromiso extranodal ocasional. El diagnóstico defini-tivo requiere inmunohistoquímica. Su comportamiento clínico, el tratamiento, así como su evolución resultan poco conocidos. Presentamos el caso de un paciente al que se le diagnosticó un sarcoma dendrítico folicular con afectación axilar.

Folicular dendritic cell sarcoma is an extremelly rare lymphoid neoplasm. Lymph nodes are predominantly afected, but occasionallu extranodal compromise is seen. Definitive diagnosis requires confirmaton by inmunohistochemistry. The clinical features and management are not well know. We present the case follicular dendritic cell sarcoma with axilary afectaton.

Histiocitosis de células de Langerhans: el "camaleón" de la dermatopediatría / Langerhans cell histiocytosis

La Histiocitosis de Células de Langerhans (HCL) es una neoplasia mieloide de las células dendríticas Langerhans (CDL), caracterizada por acúmulos de células dendríticas mieloides CD207+. Corresponden a un espectro de enfermedades, desde sólo cutáneas a variantes multiorgánicas. El objetivo de este reporte es describir el caso clínico de un paciente pediátrico, con diagnóstico de Histiocitosis de Células de Langerhans, enfatizando el algoritmo clínico. Paciente masculino de 1 año y 5 meses, con antecedentes de otorrea persistente, refractaria a tratamiento, de un año de evolución. Consulta en policlínico de dermatología por "dermatitis severa" desde hace 1 año. Al examen físico se constatan lesiones tipo dermatitis seborreica generalizadas en tronco y cuero cabelludo, intertrigo fisurado, pápulas eritemato-costrosas plantares con petequias y pus en conducto auditivo externo bilateral. Presenta Hemoglobina 9,5 mg/dl, Hematocrito31,9%, leucocitos 12.400, linfocitos 33,3%, plaquetas 920.000, VHS 27. Subpoblaciones linfocitarias: CD3: 34,7%, C4: 22,7%, CD8: 9,7%, CD19:47,8%. HTLV negativo, VIH negativo. Acaro-test negativo. Dermatopatología: Denso infiltrado de células linfomonocíticas en dermis papilar, con ensanchamiento de estas y gran epidermotropismo, con abundante citoplasma eosinófilo con núcleos arriñonados, CD1a y langerina positivo. Recomendamos elevar la sospecha diagnóstica ante un cuadro de dermatitis seborreica generalizada que esta fuera del rango etario característico y en casos de dermatitis refractarias, donde a pesar de un adecuado tratamiento médico, el paciente persiste comprometido.

Langerhans Cell Histiocytosis (HCL) is a myeloid neoplasm of Langerhans dendritic cells (CDL), characterized by accumulations of myeloid dendritic cells CD207 +. They correspond to a spectrum of diseases, from cutaneous to multi-organ variants. The objective of this report is to describe the clinical case of a pediatric patient with diagnosis of, emphasizing the clinical algorithm. Male patient,1 year and 5 months old, with a history of refractory persistent otorrhea, consulted because of long term severe dermatitis. Physical examination revealed generalized seborrheic dermatitis lesions on the trunk and scalp, cleft intertrigo, plantar erythematous-crusted papules with petechiae, and pus in the external auditory canal. Laboratory findings showed: Hemoglobin 9.5 mg / dl, Hematocrit: 31.9%, leukocytes: 12,400, lymphocytes 33.3%, platelets: 920,000, HSV 27. Lymphocyte subpopulations: CD3: 34.7%, C4: 22.7%, CD8: 9.7%, CD19: 47.8%. HTLV negative, HIV negative. Scabies Negative. Dermatopathology: Dense infiltrate of lymphomonocytic cells in the papillary dermis with widening of the papilla and large epidermotropism, cells show abundant eosinophilic cytoplasm with "kidney nuclei", CD1a and langerin were positive. We recommend elevating the diagnostic suspicion in the face of a generalized seborrheic dermatitis that is outside the characteristic age range and in cases of refractory dermatitis, where the patient persists compromised.

Papel de la vía de señalización Notch en la diferenciación de las células inmunes / Role of Notch signaling pathway in the differentiation of immune cells

Resumen La vía de señalización Notch es una vía conservada evolutivamente y está involucrada en el control de diversos eventos durante el desarrollo de las células eucariotas. Esta vía se ha relacionado con la expresión y la diferenciación de las células inmunes; por lo tanto, su activación es fundamental en la expresión de la respuesta inmune innata y adquirida, que permite a los mamíferos defenderse frente antígenos externos.

Abstract The Notch signaling pathway is evolutionarily preserved and is involved in the control of several events during the development of eukaryotic cells. This pathway has been linked to expression and differentiation of immune cells, therefore it´s activation is critical in the expression of the innate immune and acquired response that allows mammals to defend themselves against external antigens.

Células dendríticas e interferones en el lupus eritematoso sistémico / Dendritic cells and interferons in systemic lupus erythematosus

Resumen El lupus eritematoso sistémico (LES) es un trastorno autoinmune con base genética, caracterizado por la aparición de autoanticuerpos, formación y depósito de complejos inmunes circulantes e inflamación crónica en varios órganos. La etiología es multifactorial y, en individuos genéticamente predispuestos, factores medioambientales y componentes hormonales juegan un rol clave en el sistema inmune de esta enfermedad. Cerca de 25 loci genéticos han sido identificados, indicando la importancia en esta enfermedad; sin embargo, la tasa de concordancia para el LES es de tan solo el 25% entre gemelos monocigotos (1,2). Un ejemplo de ello son las deficiencias de los componentes iniciales en la vía clásica del complemento sérico como el C1q, C2 o C4, que si bien es infrecuente, confieren susceptibilidad genética para el LES en una tasa del 30% en caso de deficiencia del C4 y de más del 90% para una deficiencia del C1q (3). Por otro lado, se demostró que el C1q inhibe a las células dendríticas plasmocitoides (CDP) en la secreción de interferón alfa (IFN-a), proporcionando así un nuevo enlace entre la deficiencia del complemento y la activación de la vía del IFN (4). Por ello, el IFN-a es considerado como un actor central en la patogénesis del LES, encontrándose concentraciones séricas altas en los brotes de esta enfermedad (5). En consecuencia, estos IFN ejercen efectos claves en la fisiopatología del LES, lo que sugiere que esta citoquina no solo posee un efecto a nivel del sistema inmune innato, sino también en las respuestas inmunes adaptativas. Teniendo en cuenta estos hechos, se puede anticipar que las CDP, fuente principal de secreción de IFN, están involucradas en dicha enfermedad autoinmune. En esta revisión nos centraremos en la participación de las CDP y del IFN en el LES (6,7).

Abstract Systemic Lupus Erythematosus (SLE) is an autoimmune disorder with a genetic basis, and is characterised by the appearance of autoantibodies, the formation and deposition of circulating immune complexes, and chronic inflammation in various organs. It is of multifactorial origin, and in genetically predisposed individuals, environmental factors and hormonal components play a key role in the immune system of the disease. About 25 genetic loci have been identified, indicating the importance in this pathology. However, the concordance rate for SLE is only 25% among monozygotic twins. An example of this is the deficiencies of the initial components in the classical serum complement pathway such as C1q, C2 or C4, which, although rare, confer genetic susceptibility for SLE at a rate of 30% in the case of C4 deficiency, and more than 90% for C1q deficiency. It was also demonstrated that C1q inhibits plasmacytoid dendritic cells (pDCs) in the secretion of interferon-alpha (IFN-a), thus providing a new link between complement deficiency and activation of the IFN pathway. Therefore, IFN-a is considered to have a central role in the pathogenesis of SLE, with high serum concentrations being found in outbreaks of this disease. These IFN exert prominent immunoregulatory effects, suggesting that this cytokine is key, not only in the innate immune system, but also in adaptive immune responses. Taking these facts into account, it can be anticipated that pDCs, the main source of IFN secretion, are involved in this autoimmune disease. In this review, we will focus on the participation of pDCs and IFNs in SLE.

Sarcoma diseminado de células dendríticas interdigitantes / Disseminated interdigitating dendritic cell sarcoma

Se describe el caso de una mujer de 70 años que consultó por dolor abdominal asociado a pérdida de peso y sudoración nocturna. En el examen físico se destacaban una masa abdominal comprendida entre el epigastrio y el flanco izquierdo, de unos 5 cm de diámetro, duro-elástica, móvil e indolora, y al menos tres adenopatías supraclaviculares bilaterales de 2 cm de diámetro, duras y adheridas a planos profundos. Se realizó una biopsia de la masa abdominal, con lo que se diagnosticó un sarcoma de células dendríticas interdigitantes. Se inició quimioterapia con el esquema CHOP (ciclofosfamida, doxorrubicina, vincristina y prednisona). Falleció luego de completado el primer ciclo del tratamiento, a los seis meses del diagnóstico.

A 70 year-old woman was admitted to our hospital with a 3-month history of abdominal pain, weight loss and night sweats. On physical examination, she presented with a 5 cm diameter abdominal mass extended from epigastrium to the left flank, and at least three bilateral supraclavicular adenopathies. A disseminated interdigitating dendritic cell sarcoma was diagnosed through a biopsy of the abdominal mass. After that, a CHOP regime (cyclophosphamide, doxorubicin, vincristine and prednisone) was iniciated. She died after completion of the first cycle of treatment, six months after diagnosis.

Papel de las células dendríticas en la infección por el virus dengue: blancos de replicación y respuesta inmune / Role of dendritic cells in infection by dengue virus: targets for replication and immune response

Dengue fever, caused by dengue virus (DENV) infection, is one of the most important diseases in the world, not only due to the high morbidity/mortality rates it causes, but also because of its great economic and social impact in tropical/subtropical countries. DENV infection has a wide range of clinical manifestations ranging from asymptomatic infection or infection with mild symptoms to severe dengue that can lead to death. At present, no etiological treatment or effective globally distributed vaccine against the four DENV serotypes exists. Despite great efforts made to understand the mechanism associated with DENV disease pathogenesis the causes leading to severe dengue presentation have not been clarified. Some hypotheses seek to give a biological and physiological explanation to the clinical manifestations that appear during the infection. Based on the evidence that after contact with dendritic cells DENV alters the functionality of these cells, this review aims to describe the most relevant findings regarding the importance of dendritic cells in the context of DENV infection and progression of the illness.

El dengue, causada por el virus dengue (DENV), es una de las enfermedades más importantes no sólo por los altos índices de morbilidad/mortalidad, sino también por su gran impacto económico y social en los países de las regiones tropicales/subtropicales. La infección por el DENV cursa por un variado rango de manifestaciones clínicas que van desde una infección asintomática o con síntomas leves, hasta el dengue grave que puede ser fatal. En la actualidad, no se dispone de un tratamiento etiológico y tampoco de una vacuna eficaz mundialmente distribuida, contra los 4 serotipos del DENV. A pesar de los grandes esfuerzos orientados a entender el mecanismo asociado con la patogénesis de la enfermedad, aún no se ha logrado esclarecer de forma definitiva las causas que conllevan a las formas graves de enfermedad. Algunas hipótesis buscan dar una explicación biológica y fisiológica a las manifestaciones clínicas que se presentan durante la infección. Dado que una de ellas sugiere que luego del contacto con las células dendríticas el DENV altera su funcionalidad, la presente revisión tiene como objetivo describir los hallazgos más relevantes referentes a la importancia de dichas células en el marco de la infección por el DENV y progresión de la enfermedad.

Vacunas terapéuticas antitumorales basadas en células dendríticas / Dendritic cell-based therapeutic cancer vaccines

En los últimos años la inmunoterapia ha revolucionado el tratamiento de pacientes con cáncer avanzado. El mayor conocimiento de la biología tumoral y de la inmunología ha permitido desarrollar tratamientos racionales manipulando el sistema inmunitario con importante impacto clínico. Entre otras estrategias de inmunoterapia contra el cáncer se ha explorado el uso de vacunas terapéuticas basadas en células dendríticas (CD). Las CD son células de origen hematopoyético, que expresan constitutivamente moléculas presentadoras de antígeno, y son funcionalmente las inductoras más potentes de la activación y proliferación de linfocitos T a los que presentan antígenos. Los linfocitos T CD8+ proliferan y adquieren capacidad citotóxica cuando reconocen su antígeno específico presentado en la superficie de CD, aunque solo algunos tipos de CD pueden presentar antígenos internalizados desde el exterior celular a precursores de linfocitos T citotóxicos (a esta función se la llama presentación cruzada). Explotar la inducción de una respuesta inmunitaria adaptativa eficaz se considera una buena opción por su especificidad y prolongada duración de la respuesta. Las CD, gracias a su particular capacidad de presentación antigénica y de estimulación linfocitaria, son capaces de revertir la respuesta inmunitaria antitumoral deficiente que presentan algunos pacientes con cáncer. Las CD se pueden obtener a partir de distintas fuentes, empleando diversos protocolos para generar diferenciación y maduración, y se administran por diversas vías como son subcutánea, intravenosa o intranodal. La gran variedad de protocolos en los que se aplican las CD explica los resultados clínicos tan heterogéneos que se han comunicado hasta la fecha.

In recent years immunotherapy has revolutionized the treatment of patients with advanced cancer. The increased knowledge in the tumor immune-biology has allowed developing rational treatments by manipulation of the immune system with significant clinical impact. This rapid development has significantly changed the prognosis of many tumors without treatment options up to date. Other strategies have explored the use of therapeutic vaccines based on dendritic cells (DC) by inducing antitumor immunity. DC are cells of hematopoietic origin, constitutively expressing molecules capable to present antigens, that are functionally the most potent inducers of the activation and proliferation of antigen specific T lymphocytes. The CD8+ T cells proliferate and acquire cytotoxic capacity after recognizing their specific antigen presented on the surface of DC, although only some types of DC can present antigens internalized from outside the cell to precursors of cytotoxic T lymphocytes (this function is called cross-presentation) requiring translocation mechanisms of complex antigens. The induction of an effective adaptive immune response is considered a good option given its specificity, and prolonged duration of response. The DC, thanks to its particular ability of antigen presentation and lymphocyte stimulation, are able to reverse the poor antitumor immune response experienced by patients with cancer. The DC can be obtained from various sources, using different protocols to generate differentiation and maturation, and are administered by various routes such as subcutaneous, intravenous or intranodal. The wide variety of protocols resulted in heterogeneous clinical responses.