Evaluation of levels of inflammatory markers, growth factors and PD-L1 and Epstein-Barr virus infection in patients with Classical Hodgkin Lymphoma: a prospective study

• Grant number: 24/06015-4
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Vitor Bonetti Valente
• Grantee: Vitor Bonetti Valente
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated researchers: Daniel Galera Bernabé ; Felipe Paiva Fonseca ; Glauco Issamu Miyahara ; José Cândido Caldeira Xavier Júnior ; Sandra Helena Penha de Oliveira

Abstract

Classical Hodgkin Lymphoma (CHL) is a lymphoproliferative malignancy of B lymphocytes associated with Epstein-Barr virus (EBV) infection and modulated by proinflammatory cytokines and chemokines and growth factors. The production and secretion of these inflammatory mediators by Hodgkin and Reed-Sternberg cells in the tumor microenvironment can lead to CHL progression. This clinical progression compromises the patient's quality of life, increases the risk of recurrence or refractory disease and reduces the chance of cure. Although some evidence demonstrates differences in systemic and tumor levels of molecules related to CHL progression, to our knowledge, there are still no studies that have investigated the concentrations of these mediators and the presence of EBV in the saliva of patients with the disease. The aim of the present study is to analyze the levels of inflammatory markers, growth factors and PD-L1 and EBV infection in CHL patients before oncological treatment. The study will include 30 patients diagnosed with LHC and 30 healthy volunteers. The patients will come from the Oral Oncology Center of the Araçatuba School of Dentistry, the Oncology Treatment Center of the Santa Casa Hospital of Araçatuba and the Base Hospital of São José do Rio Preto. Blood and saliva samples from LHC patients and healthy volunteers will be collected at the time of admission to the study. Plasma and salivary levels of cytokines (IL6, IL15 and IL17), chemokines (CCL5, CCL17 and CCL22), growth factors (TNF¿, TGF¿ and VEGF) and the immune checkpoint inhibitor PD-L1 will be measured using the Multiplex® assay. The presence of EBV in tumor tissue samples and saliva of LHC patients will be investigated using in situ hybridization and RT-PCR techniques, respectively. The presence of EBV will also be investigated in the saliva of healthy volunteers. Demographic, clinicopathological and biobehavioral data of LHC patients and healthy volunteers will be collected from a specific clinical record. Differences between the groups in relation to plasma and salivary levels of proinflammatory cytokines and chemokines, growth factors and PD-L1 will be analyzed. In addition, differences between the groups regarding the presence of EBV in saliva will also be evaluated. The profile of LHC patients and healthy volunteers will be matched according to their demographic, clinicopathological and biobehavioral characteristics. In the group of LHC patients, the association of demographic, clinicopathological and biobehavioral data with plasma and salivary levels of inflammatory markers, growth factors and PD-L1 and the presence of EBV in the tumor and saliva will be investigated. The data will be checked for normality and statistical analysis will be performed using specific tests. For continuous data, the results will be presented as mean ± standard error of the mean (SEM). The critical level will be set at 5% (p<0.05) to admit differences in values as statistically significant. (AU)