The influence of Epstein-Barr virus in the microenvironment of classic Hodgkin lymphoma: A focus on T-cells and macrophages

Background The prominent immune landscape in classic Hodgkin lymphoma is an essential tool to understand the pathogenesis of the disease. Objective The aim of this study was to evaluate the influence of the Epstein-Barr virus on the frequency and spatial distribution of lymphoid T-cells and macrophages in the immune microenvironment. Methods Pre-treatment lymph node biopsies of 54 Epstein-Barr virus-positive and 91 virus-negative cases of classic Hodgkin lymphoma were studied. Different immune subsets, such as macrophages, T-helper, T-follicular helper, T-regulatory, and T-cytotoxic cells, were evaluated by digital image analysis according to their position in areas close to or distant from neoplastic cells. Results When compared to virus-negative cases, Epstein-Barr virus-positive classic Hodgkin lymphoma exhibited a higher prevalence of macrophages and CD8 + T-cells in both close and distant areas. Furthermore, CD4 + T-cells in distant areas and their subpopulations (T-regulatory and T-follicular helper) were diminished (p-values: CD68 close: p = 0.028, distant: p = 0.022; CD163 close p < 0.001, distant p = 0.003; CD8 close and distant p < 0.001; CD4 distant: p = 0.04). Clinically, Epstein-Barr virus-positive patients were older by a decade and had a higher stage of disease when compared to virus-negative cases. No associations of viral status with refractoriness to treatment, recurrence, or disease-related death were observed. Conclusions Cases of Epstein-Barr virus-positive classic Hodgkin lymphoma are related to a cytotoxic predominance, a significant macrophage component, and a decrease in T-follicular helper and T-regulatory cell populations compared to virus-negative cases.