Spatial transcriptomics of HIV-associated non-Hodgkin lymphomas by EBV status and cell of origin

Non-Hodgkin Lymphoma (NHL) is the main cancer-related mortality for people living with HIV (PLWH), who have elevated risk for lymphoma relative to the general population. NHL genetic and molecular classifications have been intensely studied and correlated with clinical outcomes, but critical unanswered questions relevant to malignancy persist. For example, tumors positive for Epstein-Barr virus (EBV) account for 30-50% of HIV-associated NHLs, are particularly aggressive, and have poorer clinical outcomes – yet insights on the nature of EBV in NHL pathogenesis or potential therapeutic vulnerabilities have been limited. Here, we examined HIV-associated NHLs stratified by cell of origin (COO), molecular subtype, and EBV status using genome-wide spatial transcriptomic analyses. Overall design: FFPE sections from ten different HIV-associated non-Hodgkin lymphoma (HIV-NHL) biopsies were analyzed with the 10x Genomics Visium V2 platform in this study. Five of the biopsied tumors were positive for Epstein-Barr virus (EBV) and five were EBV-negative. Tumors from different cells of origin (e.g., germinal center B cells, plasmablasts) were incldued in both EBV-postiive and EBV-negative sample subsets.