The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased (P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease (P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer.
Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.
CIN recurrence was associated with glandular involvement and compromised margins in cone biopsy and HIV infection. The presence of CpG islands hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN recurrence.
Abstract. The production of cytokines by helper T lymphocytes is a critical event in the immune response, as alterations in the regulation of this process may result in an appropriate immune response, persistent infection or the development of autoimmune disease. Previously, this group has used flow cytometry to demonstrate the expression of interleukin-12 (IL-12) in peripheral blood CD4+ T lymphocytes from patients and mice with advanced cancer. The aim of the present study was to investigate whether CD4+ T lymphocytes from the peripheral blood (PB) of patients with cancer produce IL-12, using molecular approaches, flow cytometry and cellular imaging techniques. CD3+ and CD4+ cells, and cells producing IL-12, were isolated from the PB obtained from patients with cancer, using a cell sorting flow cytometry technique. The positivity of cells for CD3, CD4 and IL-12, which were identified by cell sorting, was visualized using immunofluorescent cellular imaging. Total RNA was extracted from the CD3+CD4+IL-12+ cells, obtained by cell sorting, for confirmation of the presence of IL-12 mRNA, using reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR demonstrated the presence of IL-12 mRNA in all patients (n=14), in contrast to the control group, in whom IL-12 expression was not detected. Immunofluorescent analysis of CD4+ T lymphocytes showed positive intracytoplasmatic IL-12 staining. These results demonstrated that CD3+CD4+ T lymphocytes in the PB of patients with cancer have the capacity to synthesize and express IL-12.
O câncer de esôfago é uma importante enfermidade, principalmente, para o sexo masculino, tendo, segundo o INCA (Instituto Nacional de Câncer), uma estimativa de mais de 10 mil novos casos por ano, sendo mais de 8 mil atribuídos a este grupo. Assim como nos demais tipos de câncer, é axiomática a importância de obter o diagnóstico precoce, porém, aqui se encontra um desafio desse quadro: em sua fase inicial, é assintomático ou apresenta sintomas inespecíficos. Dentre os fatores de risco, pode-se destacar o tabagismo e o consumo frequente de bebidas muito quentes. Esse estudo objetiva analisar o número de internações, em caráter de urgência, de pacientes acometidos por neoplasias malignas do esôfago no Brasil entre jan/2015 e abr/2019, fazendo um comparativo entre as regiões brasileiras. 2 METODOLOGIA Trata-se de um estudo epidemiológico retrospectivo com análise comparativa baseado nos dados de internações por neoplasias malignas do esôfago por região do Brasil registrados no DATASUS no período de janeiro de 2015 a abril de 2019. 3 RESULTADO E DISCUSSÃO O número de internações foi de 1.156 na região Norte, 7.518 na região Nordeste, 30.131 na região Sudeste, 15.012 na região Sul e 3.109 na região Centro-Oeste, totalizando 56.926 internações. A partir dos dados, foi evidenciada uma grande disparidade no número de casos ao comparar as regiões sul e sudeste com as demais. Tendo em vista que os principais fatores de risco são o tabagismo e o consumo frequente de bebidas quentes (65 °C ou mais) e que esses são comumente usados pela população como alternativas ao frio, a disparidade pode ser explicada segundo dados do IBGE (Instituto Brasileiro de Geografia e Estatística), que mostram que essas regiões apresentam as temperaturas médias anuais mais baixas do país, sendo mais extremas na região sul. Além disso, dados do INCA demonstram que a região sul apresenta a maior proporção de fumantes de tabaco com 18 anos ou mais no Brasil, sendo seguida pela região sudeste. Nesse contexto, pode-se destacar ainda o consumo do chimarrão ou mate, uma bebida característica da cultura do Cone Sul e que é composto por uma cuia, uma bomba, erva-mate moída e água a aproximadamente 70 graus Celsius. Desprende-se do exposto que os habitantes das regiões Sul e Sudeste além de serem mais acometidos, representam um grupo de risco para essa enfermidade, principalmente, pelos hábitos de vida. Sendo assim, conclui-se que mudanças nos hábitos e rastreio precoce representam a melhor alternativa para frear o avanço no número de casos de neoplasias malignas no esôfago.
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