Exploration of T-cell composition and exhaustion profile of Brazilian patients with diffuse large B-cell lymphoma stratified by self-declared ethnicity

• Grant number: 25/24922-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Carmino Antonio de Souza
• Grantee: Maria Júlia Couto Maris-Guia
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera), AP.CEPID

Abstract

Diffuse large B-cell lymphoma is a malignant and aggressive neoplasm that accounts for approximately 30% to 40% of non-Hodgkin lymphoma cases in the Western world. It is a heterogeneous tumor in its clinical and histological manifestations. Of particular interest is the ethnic composition of patients, as a predominance of diagnoses at more advanced stages is seen in afrodescendant patients compared to white patients. In addition to possible socioeconomic influences, such a discrepancy may be linked to biological factors, given the higher frequency of mutations in certain genes essential for DNA maintenance, such as ATM, SETD2 and TET2, in black patients, when compared to the others. From this perspective, the tumor microenvironment is a particularly valuable tool in investigating the determining role of ethnicity in the patient's condition. Preliminary data suggest that these mutations seem to enable a senescence-associated phenotype (SASP) in tumor cells, which may shift immune response to an anergic pole. Importantly, exhaustion of T-cells in other tumor types is a phenomenon linked to SASP, However, data concerning T-cell profiles among distinct ethnic groups in DLBCL are still lacking.Thus, the study will aim to investigate the presence and impact of T-cell composition and exhustion profiles in DLBCL biopsy samples, with a particular focus on comparing White and Brown/Black individuals. To achieve this, a retrospective study will be conducted using archived biopsy specimens from patients followed at Unicamp between 2015 and 2025. T-cells will be detected with immunohistochemistry by using antibodies against CD4, CD8, TIM3 and LAG3. The results will be correlated with clinical, ethnic, and therapeutic outcome data, aiming to determine whether the biomarkers are correlated and behave as differential prognostic markers between ethnical groups.