Navegando por Palavras-chave "hodgkin's lymphoma"

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    Avaliação dos linfócitos t cd4+ctla-4+ e do receptor da il-7 (il-7r cd127) ao diagnóstico e após o tratamento de pacientes com linfoma de hodgkin clássico
    (Universidade Federal de São Paulo (UNIFESP), 2014-05-28) Silva, Joyce Matie Kinoshita da [UNIFESP]; Baiocchi, Otavio Carvalho Guimarães [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The interaction of EBV and RS cells contribute for cytokines/chemokines expression in the microenvironment. It is believed that IL-7 and IL-7 receptor (IL-7R?; CD127) roles in lymphoid tumor pathogeneses. Regulatory T cells (T reg cells) are suppressive CD4+ cells involved role in immunosuppression of immune reactions like autoimmunity, allergy and immunopathology. CTLA-4 is one of the marker that have also been recognized as regulatory T cells, potentially decreasing antitumor immune response. Augmentation of the immune response via blockade CTLA-4 has shown an improvement in survival for patients with metastatic melanoma, which prompted the Food and Drug Administration (FDA) approval of the CTLA-4 function blocking antibody Ipilimumab for this disease. Purpose: We aimed to evaluate the expression of CTLA-4 and CD127 on CD4+ T cells in peripheral blood mononuclear cells (PBMC) of patients with classical Hodgkin lymphoma (cHL) and the impact of treatment on these cells and correlate these findings with clinical and epidemiological aspects. Patients and Methods: Peripheral blood from 19 healthy individuals and 34 patients with classical Hodgkin?s lymphoma was obtained after informed consent. Patients were submitted to treatment (quimiotherapy and/or radiotherapy) and after one month finished the treatment another sample of peripheral blood was obtained. All patients were HIV negative. Phenotype of regulatory T cells was done by flow cytometry using CD3, CD127, CD4, CTLA-4-PE, CD25. Samples were acquired using the Cell-Quest software and by FACSCalibur flow cytometer (BD Biosciences, San Jose, CA, USA). Results: From the 34 cHL patients recruited for this study, 17 (50%) were male, 16 (47%) had Epstein-Barr virus (EBV) related cHL, 27 (79%) patients presented with B symptoms and 19 (56%) patients had advanced diseases at diagnosis. The percentage of CTLA-4 expression on CD4+ T cells was significantly increased in patients with cHL at diagnosis compared with healthy controls [median 8.7 (1.9 ? 43.83) vs 2.5 (0.7 ? 26.2); p<0.001]. Additionally, the frequency of this population decreased significantly following treatment [8.7 (1.9 ? 43.83) vs 3.9 (1.5 - 30.3); p=0.043], with values similar to healthy controls (3.9 vs 2.5; p=0.009). By contrast, the frequency of CD127 expression on CD4+ T lymphocytes was decreased at diagnosis, with values increasing after therapy [41.2 (3.3 ? 75.0) vs 53.9 (17.1 ? 81.3); p=0.002], similar to healthy controls [53.9 (17.1 ? 81.3) vs 58.2 (41.2 ? 89.8); p=0.21]. The frequencies of these cells were not correlated with age, gender, disease stage, erythrocyte sedimentation rate (ESR), albumin levels and EBV status. Conclusion: In this study we showed that treatment play an important role in the immunological system of these patients reestablishment. The treatment help to decrease the expression of CTLA-4 that was found increased in the moment of diagnose comparing to healthy control, and help to increase the expression of CD127 that was decreased at diagnosis. Our data have clinical implication because the promising immunotherapy regimen targeting CTLA-4 and the use of drugs that alter CD127 signaling might be beneficial in classical Hodgkin lymphoma.
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    Perfil de citocinas pró e antiinflamatórias em pacientes com linfoma de hodgkin clássico
    (Universidade Federal de São Paulo (UNIFESP), 2014-12-18) Silva, Priscilla Brito da [UNIFESP]; Baiocchi, Otavio Carvalho Guimarães [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Classical Hodgkin?s Lymphoma (cHL) is a malignant lymphoma most commonly affecting young adults. Unlike other cancers, tumor microenvironment of cHL is composed for only 1 to 5% of malignant cells, imbibed in an inflammatory microenvironment of nonmalignant cells. Understanding the mechanisms of how tumor microenvironment of classical Hodgkin lymphoma (cHL) fosters immune privilege and survival of Hodgkin-Reed-Sternberg (HRS) cells is crucial for the development of new biomarkers and therapy strategies. Purpose: In this study, we aimed to measure serum levels of pro and anti-inflammatory cytokines in cHL patients before and after treatment compared with healthy controls group, and to investigate associations with clinical and pathologic characteristics. Methods: We prospectively studied all cases of cHL diagnosed between March 2009 to March 2013 at the Universidade Federal de São Paulo and Hospital Santa Marcelina. Additionally, 18 healthy controls were included and recruited from our University Blood Bank. Serum cytokines pro and anti-inflamatories were determined in serum of patients and control by multiplexed immunoassay system. All patients received similar treatment. Results: Twenty nine patients with cHL were evaluated, the mean age at diagnosis was 40 years and 51.7% were female. The majority of patients were classified as cHL nodular sclerosis (79.3%), had B symptoms (79.3%), had no bulky disease (55.2%), had no advanced disease (51.7%), presented altered levels of VHS and albumin (75.9% and 71.4%, respectively), had low risk according IPS (27.6%) and 62% were cHL unrelated to EBV. There was no difference between the group who relapsed and patients without recurrence. Patients with higher IPS was correlated with increased levels of IL-6 (p=0,003), sCD25 were higher in patients with low serum albumin (p=0,04) and IFN-? seemed to correlate with B symptoms, although not reaching statistical significance (p=0,057). Pre-treatment levels of IL-10, IL-6, TNF-? and sCD25 were elevated in cHL patients compared to healthy controls (p<0,001), with median values of 7 pg/mL (range: 0,3 ? 230,9), 5,3 pg/mL (range: 0,4 ? 72,7), 14,6 (range: 4,0 ? 60,4) and 575,9 pg/mL (range: 7,5 ? 1813,3), respectively. Treatment significantly reduced the levels of IL-10 (7,0 to 0,3; p<0,001), IL-6 (5,3 to 0,4; p=0,014), and sCD25 (575,9 to 93,5, p<0,001), however increased levels of IL-4 (0,6 x 2,2, p=0,002). When compared to normal controls, levels of IL-6 (0,4 to 0,4; p=0,027), sCD25 (93,5 to 7,5; p=0,002) and TNF-? (12 to 8,7; p=0,003) after treatment persisted elevated. Conclusion: In this study we showed higher levels of IL-6, IL-10, TNF-? and sCD25 in cHL patients at diagnosis than in healthy control, after treatment levels of IL-6, IL-10 and sCD25 decreased gradually but did not normalize. Additionally, elevated IL-6, sCD25 and IFN-? levels in serum correlated with some clinical and laboratory features. Understanding the cytokine pattern is extremely important in the development of future therapies that target interaction between neoplastic cells and the inflammatory microenvironment. Cytokines may be useful biomarkers for monitoring the HL disease and its response to chemotherapy