Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype among non-Hodgkin lymphomas, characterized by an aggressive behavior and molecular heterogeneity. Recent studies have shown that individuals of African descent with DLBCL present a higher incidence of advanced clinical forms and poorer therapeutic outcomes. Evidence suggests that such disparities may be related not only to social factors but also to specific genetic alterations, such as mutations in the ATM and SETD2 genes, which are frequently associated with mechanisms of tumor resistance. In this context, immunosenescence emerges as a relevant biological factor, particularly through the senescence-associated secretory phenotype (SASP), which influences the immune response toward an exhausted phenotype. The relevance of these pathways considering Brazilian DLBCL patients is still unknown. This study aimed: i) To characterize the epidemiology of Brazilian DLBCL patients, stratified by autodeclared race and geographical regions of origin; ii) To assess whether immunohistochemical expression of GLB1 (a SASP marker) and TIM3 (an imune-exhaustion marker) correlate with racial distribution and clinical features. This is a retrospective study including DLBCL patients with archived diagnostic biopsy specimens, followed at Unicamp between 2008 and 2023. Biopsies were reviewed by a hematopathologist, and representative 1mm-twin cores were selected to build a tissue microarray. Then, immunohistochemistry for the proteins GLB1 and TIM3 was performed. Staining was visually evaluated and considered positive only if >30% of tumor cells were labeled; positivity in non-neoplastic cells was not considered. Clinical data were obtained from the medical records. Statistical analyses encompassed Fisher’s exact test and chi-squared test for comparisons between categorical variables, and Mann-Whitney U test for comparisons involving numerical variables. In this preliminary sample, 125 patients were studied, encompassing 62 males (49.6%) and 63 females (50.4%). Median age at diagnosis was of 57 years old (range: 17-88). Geographical origin of the patients was variable, but the majority of the individuals (64.8%) were born in the southeast region, followed by northeast (12.8%), South (4.0%) and center-west (2.4%). In 20 cases (16.0%), this data could not be determined. Most individuals were self-declared white (90, or 72.0%), followed by brown (26, or 20.8%) and black (9, or 7.2%). At the end of the follow-up period, 24 patients (19.2%) had died. Concerning immunoexpression profiles, 25 patients (20.0%) had expression of GLB1, and 30 (24.0%) of TIM3. In addition, 12 patients (9.6%) had dual positivity of the markers, whereas 45 (36.0%) did not express any of the proteins. No associations were seen between expression of the proteins and age, sex, self-declared race or geographical region of origin (p>0.05 for all comparisons). This preliminary report shows no evidence of association between expression of GLB1 and TIM3 with sociodemographic features of DLBCL patients. However, quantitative evaluation of these markers is needed in order to evaluate the expressions more objectively, including the tumor microenvironment. Besides, a larger amount of patients, as well as exploration of other SASP and immune-exhaustion related proteins, might help to characterize biological heterogeneity of black and brown DLBCL patients.
Maris-Guia et al. (Sun,) studied this question.