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Rev. ciênc. farm. básica apl ; 43: 1-15, 20220101.
Article in English | LILACS-Express | LILACS | ID: biblio-1361855


Background/Aim: High-grade gliomas are aggressive brain neoplasms usually refractory to treatment. Recently new treatment approaches have emerged, including immunotherapies. Hence, the aim of the present study was to evaluate the efficacy and safety of immunotherapies in adult patients with high-grade gliomas. Methods: Searches were performed in three databases for relevant studies published until December 2020. Title and abstract screening, full-text review, data extraction, and risk of bias assessment were performed independently by two reviewers. Risk of bias assessment was performed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Meta-analyses were performed with Review Manager software (version 5.4.1), using risk ratio and 95% confidence intervals as measure of effect, the Mantel-Haenszel method, and random effects models. The quality of evidence assessment was conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included in the systematic review, of which 15 reported comparable data for meta-analyses. The outcomes assessed in the meta-analyses were overall survival (OS) and progression-free survival (PFS), with subgroups at 6, 12, and more than 12 months. No statistical differences were observed between immunotherapy and conventional treatment, except for the OS subgroup over 12 months. The certainty on the evidence was moderate. Conclusion: There was no evidence of an additional benefit of immunotherapy compared to standard treatment in the synthesis of results from clinical trials. Further high-quality clinical trials are needed to improve the quality of evidence concerning immunotherapies for the treatment of high-grade gliomas.

Journal of Clinical Hepatology ; (12): 457-460, 2022.
Article in Chinese | WPRIM | ID: wpr-920912


Liver-resident natural killer (LrNK) cells, as a type of newly discovered tissue-resident natural killer cells, have a strong immune killing function. During the development and progression of hepatocellular carcinoma (HCC), the function of LrNK cells is impaired and such cells may promote the progression of HCC by upregulating the expression of related immune checkpoints. Based on the latest research, this article reviews the immune function of LrNK cells and their role in the development and progression of HCC, in order to explore the application prospect of these cells in HCC immunotherapy.

Acta Pharmaceutica Sinica ; (12): 122-133, 2022.
Article in Chinese | WPRIM | ID: wpr-913177


Natural killer (NK) cells, as an essential part of innate immunity, can directly identify and kill tumor cells after being activated by the synergistic action of surface inhibitory receptors and activated receptors. It can secrete cytokines to recruit dendritic cells (DCs), induce DCs maturation and enhance adaptive immune response. It can target cancer stem cells (CSCs) and circulating tumor cells (CTCs) to inhibit cancer metastasis. NK cells have a unique inflammatory tendency, which can respond to cytokines and chemokines released from tumor sites and migrate to tumor sites, making them occupy an important advantage in cancer targeted therapy. The research on cancer targeted therapy of NK cells as drug delivery carriers, NK cell membrane-coated biomimetic nanoparticles, and NK cell extracellular vesicles (NKEVs) has attracted more and more attention. The article will focus on the mechanism of NK cells inhibiting cancer, and summarize the research progress of cancer targeted therapy of NK cells.

Acta Pharmaceutica Sinica ; (12): 76-84, 2022.
Article in Chinese | WPRIM | ID: wpr-913170


Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.

Acta Pharmaceutica Sinica ; (12): 46-63, 2022.
Article in Chinese | WPRIM | ID: wpr-913167


In recent years, immunotherapy has made great progress in clinical cancer therapy. However, the poor tumor specificity, low intra-tumoral penetration, and low cellular uptake in the systemic delivery of immunotherapeutic drugs lead to low efficacy and poor safety, limiting the development of immunotherapy. Active tumor-targeting nano drug delivery systems (aNDDS) can enhance the concentration of drugs in target cells through the interaction between surface-conjugated antibodies or ligands and the receptors on target cell membranes, providing a viable strategy for specific and efficient drug delivery. In addition, some specific types of cell membranes with the natural targeting ability have been exploited for the construction of biomimetic nanocarriers to improve the drug delivery efficiency. In view of the many advantages of active tumor-targeting nanocarriers, researchers also have designed a series of aNDDS for promoting antitumor immune responses and proved that they improved the efficacy and safety of immunotherapy. In this review, we summarize the recent progress on aNDDS for improving the tumor immunotherapy and look forward to the main challenges and future directions in this field.

Article in Chinese | WPRIM | ID: wpr-923113


@#[Abstract] Metabolic reprogramming is one of the characteristics of tumors and an important potential target for tumor therapy. The effect of the interaction between tumor and immune cells on metabolic reprogramming is one of the key factors determining the anti-tumor immune response. Tumor metabolism not only plays a key role in maintaining tumor genesis and survival, but also affects immune cells by releasing metabolites such as arginine and PGE2, thereby affecting the tumor immune microenvironment. The interaction between tumor cells and immune cells leads to metabolic competition in the tumor immune microenvironment, which limits the normal metabolism of nutrients and forms an acidic environment, and ultimately leads to a weakened anti-tumor immune response and the formation of an immunosuppressive microenvironment. Moreover, there are alterations in metabolism of immune cells during the process of immune responses, that is metabolic reprogramming occurs in immune cells during their proliferation, differentiation and performance of cellular functions. Therefore, understanding the regulatory mechanism of metabolic reprogramming of tumor cells and immune cells in tumor immune microenvironment will enable researchers to find therapeutic means of targeting metabolic pathways in anti-tumor immunotherapy.

China Pharmacy ; (12): 758-763, 2022.
Article in Chinese | WPRIM | ID: wpr-923015


The re gulators of renin-angiotensin system (RAS) include renin inhibitors ,angiotensin converting enzyme inhibitors,angiotensin Ⅱ receptor blockers ,angiotensin Ⅱ receptor agonists and angiotensin 1-7. This paper summarizes and analyzes the adjuvant effects of RAS regulators on antitumor drugs by searching the literature published from January 1992 to June 2021. The regulators of RAS can reduce the cardiotoxicity ,hematological toxicity and peripheral neurotoxicity of antitumor drugs , and has renal protective effect ;the regulators of RAS combined with other chemotherapy drugs show favorable effects on promoting chemotherapeutic drugs delivery ,improving anti-angiogenesis and bypass activation of targeted drugs ,enhancing tumor immune response of immune checkpoint inhibitors ,so as to improve therapeutic efficacy of antitumor drugs. The combination of RAS regulators with antitumor drugs is expected to reduce the side effects of antitumor drugs ,enhance its efficacy and improve the prognosis of patients.

Acta Pharmaceutica Sinica ; (12): 385-391, 2022.
Article in Chinese | WPRIM | ID: wpr-922909


The potential application of dendritic cells (DC) sensitized with cytosine-phosphoric acid-guanine (CpG) oligodeoxynucleotide (ODN) and tumor antigen as a vaccine against murine melanoma was investigated with freshly isolated mouse bone marrow-derived dendritic cells. For the DC vaccine preparation, DC were sensitized with the B16 tumor antigen and CpG ODN was used to promote further maturation of the DC. The immunogenic activity of the vaccine was evaluated in vitro by determining the proliferation of T lymphocytes and the killing effect of cytotoxic T lymphocytes (CTL) on B16 tumor cells. The DC vaccine was injected intraperitoneally and tumor inhibition in mice bearing B16 xenografts was examined. All mice were cared for under an approved SIMM Institutional Animal Care and Use Committee (IACUC) protocol. In vitro, this DC vaccine promoted the proliferation of T lymphocytes and showed a potent killing effect on the target B16 cells. In vivo experiments showed that after treatment or pre-immunization both the tumor volume and weight were significantly decreased. The DC vaccine with CpG ODN and tumor antigen exhibited an inhibitory effect against melanoma, providing a potential method for melanoma cancer treatment.

Einstein (Säo Paulo) ; 20: eRC6367, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364787


ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

J. appl. oral sci ; 30: e20210344, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360531


Abstract Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Medisan ; 25(6)2021. tab, graf, ilus
Article in Spanish | LILACS, CUMED | ID: biblio-1356468


Introducción: El carcinoma basocelular es el tumor epitelial maligno más frecuente, pues constituye 60-80 % de todos los cánceres cutáneos. Objetivo: Determinar la respuesta al HeberFERON® en pacientes con carcinoma basocelular. Métodos: Se realizó un estudio observacional, descriptivo y longitudinal de 90 pacientes con carcinoma basocelular, a quienes se le administró HeberFERON® en el Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero de 2017 hasta diciembre de 2019. Se analizaron variables demográficas, clínicas y de respuesta al tratamiento. Resultados: La edad promedio fue de 63 años; hubo una mayor incidencia del sexo masculino (58 para 64,4 %) y el fototipo cutáneo II (56 para 62,0 %), con lesiones localizadas en la nariz (42 para 46,7 %), así como un predominio del subtipo clínico nodular (41 para 45,6 %). Se logró el control de la enfermedad en 100,0 % de la casuística. Conclusiones: El HeberFERON® resultó de gran utilidad en los pacientes con carcinoma basocelular, puesto que en más de la mitad de ellos se obtuvo una respuesta completa, con un mínimo de eventos adversos, todos leves y moderados.

Introduction: The basal cell carcinoma is the most frequent epithelial neoplasm, because it constitutes 60-80 % of all the cutaneous cancers. Objective: To determine the answer to HeberFERON® in patients with basal cell carcinoma. Methods: An observational, descriptive and longitudinal study of 90 patients with basal cell carcinoma to whom HeberFERON® was administered was carried out at Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from January, 2017 to December, 2019. Some demographic, clinical variables that responded to the treatment were analyzed. Results: The average age was 63 years; there was a higher incidence of the male sex (58 for 64.4 %) and the cutaneous fototype II (56 for 62.0 %), with lesions located in the nose (42 for 46.7 %), as well as a prevalence of the nodular clinical subtype (41 for 45.6 %). The control of the disease was achieved in 100.0 % of the case material. Conclusions: The HeberFERON® was very useful in patients with basal cell carcinoma, since in more than a half of them a complete response was obtained, with a minimum of adverse events, all of them light and moderate.

Skin Neoplasms , Carcinoma, Basal Cell/therapy , Immunotherapy
Rev. Rede cuid. saúde ; 15(2): [96-104], dez. 2021.
Article in Portuguese | LILACS | ID: biblio-1349497


A neoplasia maligna do pulmão é um dos tipos mais comuns e graves de câncer, sendo o que mais leva ao óbito em todo o mundo. O risco para o desenvolvimento desta doença depende da interação entre a exposição ao agente e a suscetibilidade individual para seu aparecimento. Acomete mais o sexo masculino e seu principal fator predisponente é o tabagismo. O objetivo deste artigo consiste em discutir a eficácia do medicamento Nivolumab no tratamento de câncer de pulmão de células não pequenas e evidenciar a imunoterapia como um tratamento promissor do câncer. Para tal, foi realizado um levantamento bibliográfico, utilizando-se como descritor: fatores de risco, câncer de pulmão, câncer de pulmão de não pequenas células em livros, artigos e revistas nas seguintes bases de dados: SCIELO, ANVISA, Periódicos da CAPES, Google Acadêmico. Em seguida, foi feita uma leitura analítica para ordenar as informações e identificar o objeto de estudo. Podemos perceber que a imunoterapia é bastante promissora, não só no tratamento do câncer de pulmão, como em muitos outros. O medicamento estudado, nivolumab, obteve ótimos resultados no tratamento de CPNPC, porém é notório que ainda falta estímulo para que o mesmo seja utilizado como primeira opção no tratamento de segunda linha do CPNPC.

Malignant neoplasm of the lung is one of the most common and serious types of cancer, and is the most deadly in the world. The risk for the development of this disease depends on the interaction between the exposure to the agent and the individual susceptibility to its onset. It affects males more and its main predisposing factor is smoking. The objective of this article is to discuss the efficacy of the drug Nivolumab in the treatment of non-small cell lung cancer and to evidence immunotherapy as a promising treatment for cancer. For that, a bibliographic survey was carried out, using as descriptor: risk factors, lung cancer, non-small cell lung cancer in books, articles and journals in the following databases: SCIELO, ANVISA, CAPES Periodicals, Google Scholar. Then, an analytical reading was made to sort the information and identify the object of study. We can see that immunotherapy is very promising, not only in the treatment of lung cancer, but also in many others. The medicament studied, nivolumab, obtained excellent results in the treatment of NSCLC, but it is well known that there is still a lack of stimulation for it to be used as the first option in the second line treatment of NSCLC.

Humans , Male , Female , Tobacco Use Disorder , Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms
Rev. enferm. UERJ ; 29: e58363, jan.-dez. 2021.
Article in English, Portuguese | LILACS-Express | LILACS | ID: biblio-1348774


Objetivo: analisar as reações adversas nos pacientes oncológicos em uso de inibidores de checkpoint e sua prevalência. Método: revisão integrativa da literatura, utilizando a combinação de descritores "Imunoterapia" AND "Reação adversa" AND "Neoplasias", no recorte temporal de cinco anos, incluindo as bases CINAHL (Cumulative Index to Nursing and Allied Health Literature), CINAHL (Cumulative Index to Nursing and Allied Health Literature) e Cochrane. Resultados: foram encontrados 17 artigos, sendo 14 da base de dados MEDLINE e três da base de dados CINAHL, todos na língua inglesa. As principais reações adversas identificadas foram diarreia, colite, pneumonite, fadiga, rush, alterações hepáticas e endócrinas. Os artigos revelaram maiores prevalências dessas reações quando o tratamento está associado às medicações Nivolumabe e Ipilimumabe juntas, sendo observadas em cerca de 42% a 57% dos pacientes. Conclusão: com a rápida expansão do uso dos inibidores de checkpoint, uma terapêutica que aumenta a sobrevida desses pacientes, conhecer seus eventos adversos torna-se primordial para um cuidado de qualidade.

Objective: to examine for adverse reactions and determine their prevalence in cancer patients using checkpoint inhibitors. Method: this integrative literature review used a combination of the descriptors: "immunotherapy" AND "adverse reaction" AND "Neoplasms", in a five-year time frame, in the MEDLINE and Cochrane databases. Results: seventeen articles, all in English, were found (14 in MEDLINE and three in CINAHL). The main adverse reactions identified were diarrhea, colitis, pneumonitis, fatigue, rush, hepatic, and endocrine changes. The articles revealed that, when the treatment involved Nivolumab and Ipilimumab together, prevalence of these reactions was higher (from 42% to 57% of patients). Conclusion: with the rapid expansion of the use of checkpoint inhibitors, a therapy that increases survival, knowing their adverse events becomes essential for quality care.

Objetivo: analizar reacciones adversas en pacientes con cáncer, utilizando inhibidores de checkpoint y su prevalencia. Método: revisión integradora de la literatura, utilizando la combinación de descriptores "Inmunoterapia" y 'Reacción adversa" y "Neoplasias", en un recorte temporal de cinco años, incluyendo las bases de datos CINAHL (Cumulative Index to Nursing and Allied Health Literature y Cochrane. Resultados: se encontraron 17 artículos, siendo 14 de la base de datos MEDLINE y 3 de la base de datos CINAHL, todos en inglés. Las principales reacciones adversas identificadas fueron diarrea, colitis, neumonitis, fatiga, erupción cutánea, alteraciones hepáticas y endocrinas. Los artículos revelaron una mayor prevalencia de estas reacciones cuando el tratamiento se asocia con los medicamentos Nivolumab e Ipilimumab juntos, observándose en alrededor del 42% al 57% de los pacientes. Conclusión: con la rápida expansión del uso de inhibidores de checkpoint, una terapia que aumenta la sobrevida de esos pacientes, conocer sus eventos adversos se vuelve fundamental para una atención de calidad.

Biomédica (Bogotá) ; 41(3): 481-492, jul.-set. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1345398


Resumen Introducción. El asma es una enfermedad crónica y potencialmente grave. El 80 % de los casos es de origen alérgico, por lo cual la inmunoterapia específica con alérgenos es una alternativa terapéutica que modula el curso natural de la enfermedad. Objetivo. Evaluar el impacto de la inmunoterapia en pacientes pediátricos con asma atendidos en una institución de salud de Colombia. Materiales y métodos. Se hizo un estudio observacional descriptivo con componente analítico de corte transversal. Se incluyeron 62 pacientes con diagnóstico de asma alérgica sensibilizados a ácaros del polvo y en tratamiento, mínimo, con seis dosis de inmunoterapia contra ácaros. El efecto del tratamiento se evaluó mediante la escala de puntuación del ACT (Asthma Control Test), la escala de tratamiento de la GINA (Global Initiative for Asthma) y la espirometría. Resultados. La puntuación de la prueba ACT antes del inicio de la inmunoterapia, correspondía a 30 % de pacientes con asma no controlada, 28 % con buen control y 4 % con asma totalmente controlada. Entre los pacientes con asma no controlada, el 46,7 % logró un buen control y el 23,3 % alcanzó un control total. En cuanto a la percepción de los pacientes sobre la mejoría con la inmunoterapia, el 9,75 % percibió una mejoría menor del 50 %, el 45,2 %, una entre el 50 y el 90 %, en tanto que el 41,9 % refirió una igual o mayor del 90 %. No se encontraron cambios significativos en los valores del volumen espiratorio forzado en un segundo (VEF1) en las espirometrías. Conclusiones. Se observaron cambios significativos en los puntajes del ACT y en la percepción de mejoría de la enfermedad en la población tratada con inmunoterapia específica para ácaros, es decir, que esta tendría un efecto beneficioso en el curso natural de la enfermedad

Abstract Introduction: Asthma is a chronic and potentially serious disease and 80% of the cases have an allergic etiology. In this sense, allergen-specific immunotherapy is an alternative that modulates the natural course of the disease. Objective: To evaluate the impact of immunotherapy in pediatric asthma patients treated at a health institution in Colombia. Materials and methods: We conducted an observational descriptive study with an analytical cross-sectional component. Sixty-two patients diagnosed with allergic asthma sensitized to dust mites and treated with at least 6 doses of mite immunotherapy were included. We assessed the impact of immunotherapy using the Asthma Control Test (ACT), the Global Initiative for Asthma (GINA) treatment scale, and spirometry values. Results: The ACT score before the start reported 30% of patients with uncontrolled asthma, 28% with good control, and 4% with totally controlled asthma. Of the patients with uncontrolled asthma, 46.7% achieved good control and 23.3% total control. Regarding patients' perception of improvement with the immunotherapy, 9.75% perceived a response of less than 50%, 45.2% one between 50% -90%, and 41.9% reported response equal to or greater than 90%. No significant changes in FEV1 values were found in spirometry. Conclusions: Significant changes in the ACT scores and the perception of disease improvement were observed in the population evaluated with specific mite immunotherapy, i.e., it had a positive impact on the natural course of the disease.

Asthma , Immunotherapy , Pediatrics , Spirometry , Rhinitis , Mites
Gac. méd. Méx ; 157(3): 305-310, may.-jun. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1346111


Resumen Introducción: Los inhibidores del punto de control inmunológico (IPCi) son utilizados en los últimos años en el tratamiento de neoplasias malignas avanzadas, con ellos se ha logrado un aumento significativo de la supervivencia; sin embargo, su uso se ha asociado a incremento del riesgo de enfermedades autoinmunes. Objetivo: Describir la incidencia y las características clínicas de los pacientes tratados con IPCi que desarrollaron tiroidopatía. Métodos: Se revisaron retrospectivamente los expedientes de todos los pacientes que recibieron IPCi en los últimos tres años y se identificaron aquellos que desarrollaron anomalías tiroideas. Resultados: La prevalencia de tiroiditis fue de 7 %, con una incidencia de 21.4 % pacientes/mes. La mediana del tiempo para el desarrollo de tiroiditis fue de 63 días. La mayoría de los pacientes presentó síntomas leves o moderados y no requirió hospitalización, si bien todos menos uno desarrollaron hipotiroidismo permanente y requirieron terapia de reemplazo hormonal con levotiroxina. Conclusiones: La disfunción tiroidea secundaria a inmunoterapia es una entidad común en nuestra población. El cuadro clínico suele ser leve y no requiere suspender el tratamiento; sin embargo, debido a la alta incidencia de este evento adverso, los médicos no oncólogos deben estar familiarizados con su diagnóstico y tratamiento, para brindar un manejo multidisciplinario.

Abstract Introduction: Immune checkpoint inhibitors (ICI) are a group of drugs that have been used in recent years for the treatment of advanced malignancies such as melanoma, non-small cell lung cancer and other tumors, significantly increasing survival. However, the use of ICI has been associated with an increased risk of autoimmune diseases, with endocrine organs, specifically the thyroid, being highly susceptible to this phenomenon. Objective: To describe the incidence and clinical characteristics of patients treated with ICI who develop thyroid disease. Methods: The medical records of all patients who received ICI treatment within the last three years were retrospectively reviewed, with those who developed thyroid abnormalities being identified. Results: The prevalence of thyroiditis was 7 %, with an incidence of 21.4 % of patients-month. Median time for the development of thyroiditis was 63 days. Most patients had mild or moderate symptoms and did not require hospitalization, although all but one developed permanent hypothyroidism and required hormone replacement therapy with levothyroxine. Conclusions: Thyroid dysfunction secondary to immunotherapy is a common entity in our population. Clinical presentation is usually mild and does not require treatment discontinuation; however, due to the high incidence of these adverse events, non-oncology specialists must be familiar with the diagnosis and treatment of these alterations in order to provide multidisciplinary management.

Humans , Thyroiditis , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Incidence , Retrospective Studies , Immune Checkpoint Inhibitors
Hematol., Transfus. Cell Ther. (Impr.) ; 43(2): 185-190, Apr.-June 2021. tab, ilus
Article in English | LILACS | ID: biblio-1286676


ABSTRACT Introduction Multiple myeloma is a progressive and incurable hematological disease characterized by disordered and clonal multiplication of plasmacytes in the bone marrow. The main clinical manifestations are caused by the presence of neoplastic cells in bone tissue, as well as the excessive production of immunoglobulins and normal humoral immunity suppression. Daratumumab is an anti-CD38 monoclonal antibody that has promising results in managing the multiple myeloma disease. Objective This study aimed to investigate the scientific evidence concerning the impact of the cytomegalovirus infections in the daratumumab treatment course in extensively pretreated multiple myeloma patients. Method To this end, an integrative literature review was performed in different databases, comprising a 5-year period. Results The studies analysis revealed that the cytomegalovirus infection reactivation can occur during the use of daratumumab in multiple myeloma patients previously treated, which led to treatment discontinuation, compromised the drug efficacy and favored the disease progression. Moreover, it was observed that even with prophylactic antiviral therapy there was an infection reactivation in some cases, as well as deaths, in more severe situations. Conclusion Thus, even considering that few reports on such a topic are available in the scientific literature, the present review showed that cytomegalovirus reactivation can impair daratumumab therapy, mainly in multiple myeloma patients heavily pretreated. In addition, this study could contribute as a tool for the clinical decision and management of adverse effects in medical practices, demonstrating the importance of patient monitoring for the possibility of cytomegalovirus reactivation in heavily pretreated myeloma patients.

Humans , Cytomegalovirus Infections , Antibodies, Monoclonal , Multiple Myeloma/therapy , Virus Diseases , Review , Hematologic Neoplasms , Immune System , Immunotherapy
Medicina (B.Aires) ; 81(2): 208-213, June 2021. graf
Article in Spanish | LILACS | ID: biblio-1287272


Resumen El manejo de las reacciones adversas inducidas por los inhibidores del punto de control inmunitario (IPCI) en cáncer, demanda un trabajo multidisciplinario. Revisamos las causas y el curso clínico de las consultas e internaciones debidas a reacciones adversas de los IPCI entre septiembre de 2015 y julio de 2019 en el Instituto Alexander Fleming. Se registraron los datos demográficos, diagnóstico oncológico, reacción adversa y su grado, requerimiento de internación, tratamiento, mortalidad y evaluación de la reexposición. Se registraron 124 reacciones adversas por IPCI en 89 pacientes. Sesenta y ocho recibían monoterapia y 21 terapia combinada. Las manifestaciones cutáneas fueron las más frecuentes, seguidas de las generales, endocrinas (con mayor frecuencia hipotiroidismo), colitis, neumonitis, neurológicas y hepatitis. Fueron graves (grado ≥ 3), 26 toxicidades en 25 pacientes. Se internaron 15, y 6 de ellos requirieron terapia intensiva. Un caso fue fatal. Recibieron glucocorticoides 34 (12 de ellos por vía intravenosa). Un paciente recibió micofenolato y uno inmuno globulina endovenosa. En 20 se discontinuó el tratamiento. Ocho se reexpusieron y uno de ellos debió suspender definitivamente. Se presenta en esta serie de casos nuestra experiencia con el diagnóstico y tratamiento de las reacciones adversas de una familia de drogas cuya utilización ha crecido en los últimos años.

Abstract The management of patients with immune-related adverse events (irAEs) frequently demands a multidisciplinary approach. We reviewed the causes and clinical course of medical visits and admissions at the Instituto Alexander Fleming due to irAEs between September 2015 and July 2019. Demographic data, diagnosis, toxicity and its severity, requirement of admission, treatment, mortality, and evaluation of the re-administration of immunotherapy were collected. We found 124 irAEs in 89 patients. Sixty-eight of them received monotherapy (76.4%) and 21 (23.6%) combination of drugs. Cutaneous manifestations were the most frequent cause of irAEs, followed by general manifestations, endocrine dysfunctions (hypothyroidism the most frequent), colitis, pneumonitis, neurologic dis orders, and hepatitis. In 26 adverse events (in 25 patients), severity grade was ≥ 3. Fifteen were admitted and 6 required ICU admission. One patient died. Thirty-four received glucocorticoids, 12 of them by intravenous route. One patient received mycophenolate and one IVIG. In 20, the treatment was discontinued; 8 were re-exposed, with definitive discontinuation in one patient. In this case series we report our experience in the diagnosis and management of adverse reactions related to a family of drugs whose use has grown in recent years.

Humans , Drug-Related Side Effects and Adverse Reactions , Neoplasms/drug therapy , Nervous System Diseases , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Immunotherapy
Acta neurol. colomb ; 37(1,supl.1): 174-188, mayo 2021. tab
Article in Spanish | LILACS | ID: biblio-1248597


RESUMEN La relación entre las enfermedades inmunológicamente mediadas del sistema nervioso central (SNC) y las infecciones es muy estrecha. En primer lugar, es importante reconocer que las infecciones pueden desencadenar reacciones inmunopatológicas que pueden conducir posteriormente a la manifestación de enfermedades neurológicas. En segundo lugar, las infecciones se han reconocido como complicación de algunas de las terapias empleadas para tratar condiciones neurológicas que requieren cierto grado de inmunosupresión. Las estrategias de mitigación de riesgo (EMR) son muy importantes para prevenir complicaciones asociadas con los tratamientos farmacológicos, así como generar estrategias de prevención con respecto a inmunización y detección del perfil de riesgo, antes del inicio de terapias.

SUMMARY The relationship between immunologically mediated diseases of the central nervous system (CNS) and infections is very close. First, it is important to recognize that infections can trigger immunopathological reactions that can subsequently lead to the manifestation of neurological diseases. Second, infections have been recognized as a complication of some of the therapies used to treat neurological conditions that require some degree of immunosuppression. Risk mitigation strategies (RMS) are key in order to prevent complications associated with pharmacological treatments, as well as to generate prevention strategies with respect to immunization and detection of the risk profile, prior to starting therapies.

Rev. bras. ginecol. obstet ; 43(5): 368-373, May 2021. graf
Article in English | LILACS | ID: biblio-1288556


Abstract Objective To evaluate the antitumoral role of γδ TDC cells and αβ TDC cells in an experimental model of breast cancer. Methods Thirty female Balb/c mice were divided into 2 groups: control group (n=15) and induced-4T1 group (n=15), in which the mice received 2 x 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αβ TDC (TCRαβ+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17). Results A total of 26.53% of γδ TDC- control group (p<0.0001) - the proportion of αβ TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p<0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αβ TDC, but it decreased under conditions of tumor-related immune system response (p<0.0001). Conclusion Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

Resumo Objetivo Esclarecer o possível papel antitumoral das células TDC γδ e TDC αβ em um modelo experimental de câncer de mama. Métodos Trinta baços de camundongos Balb/c analisados por citometria de fluxo, separados entre grupo controle (n=15) e o grupo tumoral induzido por 4T1 (n=15). Resultados Presença de 26,53% de TDC γδ nos camundongos do grupo controle (p<0,0001), proporção de TDC αβ menor em células esplênicas do que TDC γδ; no entanto, estes dois tipos de células são reduzidos emcondições tumorais (p<0,0001), e a proporção de citocinas IFN-γ, TNF-α, IL-12 e IL-17 produzidas pelas célula TDC γδ foi maior do que as produzidas pelas células TDC αβ, mas foram diminuídas sob condições de resposta ao sistema imunológico relacionada ao tumor (p<0,0001). Conclusão Camundongos saudáveis induzidos ao tumor de mama 4T1 apresentaram TDC com repertório TCR γδ. Estas células expressam moléculas citotóxicas de linfócitos T, produzindo citocinas proinflamatórias anti-tumor.

Animals , Female , Mice , Breast Neoplasms/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell, alpha-beta/immunology , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Spleen/immunology , Spleen/metabolism , Interleukin-17 , Flow Cytometry , Mice, Inbred BALB C
Rev. colomb. cancerol ; 25(1): 47-55, ene.-mar. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1289198


Resumen El melanoma primario de mucosas representa el 1% de todos los cánceres. Su localización en cuello uterino es rara y existen menos de 100 casos reportados en la literatura hasta la fecha. Los datos son limitados en cuanto su estadificación y tratamiento y su pronóstico es malo con tasas de supervivencia del 10% a 5 años. Se presenta el caso clínico de una paciente de 82 años con sangrado vaginal, con evidencia de una lesión melanótica en cuello uterino, la biopsia de la lesión reportó compromiso por tumor maligno pobremente diferenciado, con inmuno perfil que confirma melanoma maligno. Los estudios de extensión no mostraron enfermedad metastásica a distancia, se presentó el caso en junta multidisciplinaria de ginecología oncológica por lo que se indicó tratamiento con radioterapia pélvica externa exclusiva con intención paliativa para control de síntomas, teniendo en cuenta: la edad, las comorbilidades y el estado funcional ECOG (Eastern Cooperative Oncology Group) 3; luego de 10 meses de seguimiento la paciente falleció.

Abstract Primary mucosal melanoma represents 1% of all cancers, the location in the cervix is rare, there are less than 100 cases reported in the literature to date, the data is limited in terms of staging and treatment, its prognosis is poor with survival rates of 10% at 5 years. We present a clinical case of a primary melanoma of the cervix in an 82-year-old patient with vaginal bleeding with evidence of a melanotic lesion in the cervix. The biopsy of the lesion reported poorly differentiated malignant tumor involvement, with an immuno-profile that favors melanoma. Extension studies were performed that did not show distant metastatic disease, the case was presented in a multidisciplinary oncological gynecology meeting, indicating treatment with exclusive external pelvic radiotherapy with palliative intention for symptom control taking into account patient comorbidities and ECOG functional status. (Eastern Cooperative Oncology Group) 3, after 10 months of follow-up the patient died.