Evaluation of regulatory and Th17 lymphocytes and its correlation with pro and antiinflammatory citoquines in patients with Classical Hodgkin lymphoma

• Grant number: 12/16864-1
• Support Opportunities: Regular Research Grants
• Duration: June 01, 2013 - February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Otavio Cesar Carvalho Guimarães Baiocchi
• Grantee: Otavio Cesar Carvalho Guimarães Baiocchi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Antônio Hugo José Fróes Marques Campos ; Gisele Wally Braga Colleoni ; Maria Mirtes Sales

Abstract

Epstein-Barr virus (EBV) can be found latently infecting Reed-Sternberg (RS) malignant cells in approximately 50% of classical Hodgkin lymphoma (cHL) patients in Brazil. EBV signaling leads to an unbalance between effector and regulatory CD4 T lymphocytes (Tregs) in the tumor microenvironment, promoting the immune evasion of RS malignant cells. Recently, our group showed that patients with EBV related cHL presented with increased Tregs in the tumor microenvironment compared with the EBV non related group (data not published yet, article submitted April 2012) However, little is known about these lymphocytes subpopulations in the peripheral blood of patients with cHL and how the presence of EBV and treatment can modify this regulatory/effector ratio. In this study, we will analyse the regulatory and effector CD4+ subpopulations in peripheral blood in patients with EBV related and non-related cHL and the impact of treatment on these cells. This is a prospective multicentric study and patienst will be recruited in the University Hospital São Paulo and University Hospital Santa Marcelina. Patients will be recruited from August 2012 to December 2013. Blood will be drawn at diagnosis and 1 to 4 months post-treatment. Twenty healthy controls will also be included in this study. Quantification of regulatory and effector T lymphocytes will be done by tissue microarray in the diagnositc materials and in the peripheral blood by flow cytometry. Gene expressing analysis will be done by Real time PCR and pro and antiinflamamtory cytokines will be measured by immune assays using the Luminex Plataform. All these data will be correlated to phenotypic and clinical parameters in uni- and multivariate models pre and post-treatment. For the present study, only cHL patients whose histology could be confirmed and EBV association established will be studied. All patients must be HIV negative and receive the ABVD chemotherapy protocol. Certainly, our study will contribute not only to our understanding on the pathogenesis of cHL but also to the development of therapeutic strategies designed to manipulate regulatory activity. Given that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones, we emphasize the importance of this Brazilian multicentric project. To the best of our knowledge, our study is the first addressing the role of EBV in Hodgkin's lymphomagenesis and CD4 homeostasis (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, PRISCILLA BRITO; PERINI, GUILHERME FLEURY; PEREIRA, LUCIANA DE ANDRADE; SACCONATO, ELYSE MORITZ; DAMASCO PENNA, ADRIANA MARQUES; GARIBALDI, JOAO; CAVALCANTE, EGYLA; BAIOCCHI, OTAVIO C. G.. Imbalance of Pro- and Anti-Inflammatory Cytokines in Patients With cHL Persists Despite Treatment Compared With Control Subjects. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, v. 15, n. 1, p. S151-S157, JUN 2015. (12/16864-1)

DA SILVA, PRISCILLA BRITO; PERINI, GUILHERME FLEURY; PEREIRA, LUCIANA DE ANDRADE; SACCONATO, ELYSE MORITZ; DAMASCO PENNA, ADRIANA MARQUES; GARIBALDI, JOAO; CAVALCANTE, EGYLA; BAIOCCHI, OTAVIO C. G.. Imbalance of Pro- and Anti-Inflammatory Cytokines in Patients With cHL Persists Despite Treatment Compared With Control Subjects. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, v. 15, p. 7-pg., 2015-06-01. (12/16864-1)

DA SILVA, PRISCILLA BRITO; REAL, JULIANA MONTE; PINTO FERREIRA, LUDMILA RODRIGUES; ESTEVES, GUSTAVO H.; BRITO, FABIO DO NASCIMENTO; BAIOCCHI, OTAVIO C. G.. Soluble PD-1 and PD-L1 as potential biomarkers for classical Hodgkin lymphoma. HEMATOLOGICAL ONCOLOGY, v. 36, n. 4, p. 709-712, OCT 2018. (12/16864-1)