cHL microenvironment in HIV infection

Human Immunodeficiency Virus (HIV)-associated lymphomas account for one of the most common co-morbidities following HIV infection, including an increased risk for classic Hodgkin lymphoma (cHL). Furthermore, the impact of HIV infection on the cHL tumor microenvironment (TME), a critical component for the tumor pathogenesis and progress, is not well understood. Here, we provide a comprehensive analysis of cHL tissues, in the presence or absence of HIV, and with respect to Epstein-Barr virus (EBV) infection, using multiplexed Immunofluorescence (mIF) and in-situ spatial transcriptomic analysis. Although HIV infection does not affect the frequencies of cancer cells, it has a significant impact on the tumor microenvironment, both at the prevalence of relevant memory CD4 and CD8 T cell subsets and possible in situ molecular pathways that could affect their functionality (e.g., TCR induced signaling). The increased prevalence of CD155high neoplastic cells supports the investigation of alternative to PD-1/PD-L1 targeted Immune Checkpoint Blockade (ICB) treatments in HIV infected cHL individuals. Furthermore, our findings indicate that the anti-retroviral treatment could affect the TME CD68 and CD163 innate immune cell subsets in treated compared to untreated HIV+EBV+ cHL. Our data reveal specific molecular targets and pathways for further investigation that could improve our understanding of possible mechanistic links between HIV and lymphomagenesis.