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.