Tumor-Specific Immunity Induced by Cryoablation in a Murine Renal Cell Carcinoma Model

PURPOSE: To evaluate tumor-specific immunity and define the mechanisms involved in the cryoimmunologic response, we compared the tumor control efficacy and immunologic responses of cryoablation with those of surgical excision in a tumor rechallenge model. MATERIALS AND METHODS: Sixty BALB/c mice with RENCA tumors that were generated in the left flank area underwent cryoablation or radical excision. The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area. The recurrence rate after tumor rechallenge in each group was then observed. To assess the immunologic response of each treatment modality, fluorescent-activated cell sorting (FACS) analysis and a cytotoxicity assay using 51Cr release were performed. RESULTS: After reinoculation of the RENCA cells, the rate of tumor growth was significantly higher in the surgical excision group than in the cryoablation group (94.4% vs. 11.1%, p=0.001). In the cryoablation group, the tumor growth rate was significantly increased after rechallenge of CT26 cells compared with RENCA (94.1% vs. 11.1%, p=0.001). The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the 51Cr release assay compared with the excision group. CONCLUSIONS: These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.

BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables. RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021). CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Cáncer de mama triple negativo: características clínicas y moleculares / Triple negative breast cancer: clinical and molecular characteristics

El cáncer de mama es una enfermedad problema en Venezuela por su incidencia, prevalencia y alta mortalidad. Representa la segunda causa de muerte por cáncer en la mujer venezolana, superado escasamente por el cáncer de cuello uterino. Los carcinomas de mama "triple negativo" se definen por falta de expresión de receptores de estrógenos, progesterona y Her2-Neu. Representan aproximadamente el 15% de todos los cáceres mamarios. Es más frecuente en mujeres pre-menopáusicas jóvenes, en latinoamericanas y en mujeres de raza negra. La mayoría de estos tumores son de tipo ductal, tienen alto grado nuclear e histológico, mayor tasa de recaídas y metástasis y peor pronóstico. La mayoría de los tumores triple negativos pertenecen al tipo molecular de los cánceres de mama tipo basal. El perfil inmunohistoquímico del cáncer de mama triple negativo ha sido investigado extensamente y es altamente heterogéneo. Estos tumores no son tratables con hormonoterapia ni con Trastuzumab y solamente se puede usar quimioterapia en el manejo sistémico. Algunos esquemas de quimioterapia son más efectivos que otros en cáncer de mama triple negativo y hay diversas terapias "emergentes" en investigación clínica.

Breast cancer is a problematic disease in Venezuela bacause of its incidence, prevalence and high mortality rate. It represents the second cause of death by cancer in the venezuelan woman exceeded slighthly by the cervix uterine cancer. Triple negative breast cancers are defined by lack of expression of estrogen, progesterone, and Her2-Neu receptors. This subgroup accounts for 15% of all types of breast cancer and for a higher percentage of breast cancer arising in young pre-menopausal Latin-American women and those of African descent. Histologically, such cancer fall into the molecular type and the basal subgroup of the breast cancer. Most of them are ductal with a high nuclear and histological grade, a higher rate of replase and metastasis and a worse prognosis. The triple negative breast cancer immunohistochemical profile has been extensively investigated and is higly heterogeneous; it is not treated with hormone therapy or with Trastuzumab and only chemotherapy in the systemic way can be used. Some chemoterapy schemes are more effective for the treatment of triple negative breast cancer and there are also "emergent" therapies in clinical investigation.

El bacilo de Calmette-Guérin como inmunomodulador en el cáncer de vejiga / The bacillus Calmette-Guérin as immunomodulator in bladder cancer

The bacillus Calmette-Guérin (BCG) is regarded as the most successful immunotherapy against superficial bladder carcinoma recurrences to date. BCG intravesical therapy for superficial bladder cancer has shown its efficacy and advantage over classical therapeutic strategies. This efficacy is based on complex and long lasting immune activation. The initial step is the binding of mycobacteria to the urothelial lining, which depends on the interaction of a fibronectin attachment protein on the bacteria surface with fibronectin in the bladder wall. Granulocytes and other immunocompetent mononuclear cells became attracted to the bladder wall and a cascade of proinflammatory cytokines sustains the immune response. In the bladder wall a largely TH1 based cytokine milieu and granuloma-like cellular foci are established. Within this scenario, the most important effector mechanisms might be the direct antitumor activity of interferons and the cytotoxic activity of NK cells. Current treatment consists of an induction phase of 6 weeks and a maintenance dose schedule of 3 weeks every three months up to 36. The majority of patients present adverse events related to dose administration due to bladder inflammatory response and on only a few ocassions, there are mayor complications like granulomatous prostatitis. Among all the neoplasms only in superficial bladder cancer the BCG is proved to be effective.

El bacilo de Calmette-Guérin (BCG) es considerado como la inmunoterapia más exitosa en contra del carcinoma de vejiga superficial recidivante hasta la fecha. La terapia intravesical con el BCG para el cáncer superficial de vejiga ha mostrado su eficacia y ventaja sobre otras estrategias terapéuticas; esta eficacia está basada en una compleja y larga duración de la activación inmunológica. El paso inicial es la unión de la micobacteria al urotelio, la cual depende de la interacción con la fibronectina de la bacteria con la fibronectina del urotelio. Los granulocitos y otras células mononucleares inmunocompetentes son atraídos hacia la pared vesical, así activando una cascada inmunológica a través de secreción de diversas citocinas, quienes estimulan a las células asesinas naturales (NK) activadas por el BCG, las cuales son capaces de diferenciar células neoplásicas y del epitelio urinario normal. En la pared vesical se encuentra un medio ambiente de citocinas principalmente del tipo TH1 y se forman focos celulares similares a granulomas. Dentro de este escenario los mecanismos efectores más importantes parecen ser la actividad antitumoral directa de los interferones y la actividad citotóxicas de las células NK. El tratamiento actual consiste en la administración intravesical del bacilo en una primera fase de inducción de seis semanas y posteriormente dosis de mantenimiento cada tres meses hasta los 36 meses. La mayoría de los pacientes presentan efectos adversos locales secundarios a la reacción inflamatoria y en un porcentaje muy pequeño se presentan complicaciones mayores como prostatitis y orquiepididimitis granulomatosa. De entre todas estas neoplasias sólo en el cáncer superficial de vejiga se han demostrado resultados satisfactorios con el empleo del BCG.

Tumor-infiltrating CD4+ T lymphocytes in early breast cancer reflect lymph node involvement

INTRODUÇÃO: O papel do sistema imunológico na patogênese e progressão do câncer de mama ainda é controverso, e isto nos estimulou a verificar a associação do imunofenótipo dos linfócitos tumor infiltrantes do câncer de mama inicial com a disseminação de células tumorais para os linfonodos axilares. MÉTODOS: Amostras tumorais de 23 pacientes com câncer de mama inicial do Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto (USP) foram obtidas no momento da biópsia e depois submetidas ao método de digestão enzimática para a extração dos linfócitos tumor infiltrantes. Os linfócitos extraídos foram analisados por citometria de fluxo com anticorpos monoclonais nas seguintes combinações: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, e CD16/56 PerCP, específicos para imunofenotipagem de linfócitos T e B, linfócitos T helper, linfócitos citotóxicos, e células Natural Killer. Os valores médios destas subpopulações leucocitárias foram comparados entre grupos de pacientes com ou sem metástases linfonodais. RESULTADOS: O valor médio do infiltrado por linfócitos T foi 24,72±17,37%, para o infiltrado por linfócitos B foi 4,22±6,27%, e para o infiltrado por células Natural Killer foi 4,41±5,22%, e para o infiltrado por linfócitos T CD4+ e CD8+ foram, respectivamente, 12,43±10,12% e 11,30±15,09%. Os valores médios do infiltrado por células T e T CD4+ foram maiores no grupo de pacientes com metástase axilar, enquanto nas outras subpopulações nada foi encontrado.CONCLUSÃO: A associação dos linfócitos T CD4+ tumor infiltrantes com metástases linfonodais sugere um papel destas células na disseminação das células neoplásicas aos linfonodos dos pacientes com câncer de mama inicial.

Aspectos inmunológicos del epitelioma basocelular / Immunologic aspects of the basal cell epitelioma

El epitelioma basocelular es el cáncer más común en humanos. Existen muchos factores involucrados en la relación huésped-tumor que determinan el aumento o la disminución de un determinado tumor. Este artículo examina algunos de estos factores, como el efecto de la radiación ultravioleta sobre la piel, el papel de células de Langerhans en el desarrollo de esta neoplasia, la respuesta inmunológica local y discute el papel de oncogenes en el epitelioma basocelular

Status of different immune cells during regression of a rat histiocytoma.

Status of CD4 and CD8 positive T-lymphocytes, natural killer cells and macrophages has been studied in animals which reject AK-5 histiocytoma. Analysis of immune cells which enter the tumour showed higher number of CD8 positive and NK cells around day 25 after tumour transplantation, suggesting their participation in tumour rejection.