Immunogenomic profiles of HIV-associated classic Hodgkin lymphoma from Malawi

This is the authors' abstract. We don't add key points for this paper.

Classic Hodgkin lymphoma (cHL) is a hematolymphoid neoplasm highly associated with Epstein-Barr virus (EBV), and molecular differences by tumor EBV status have been well characterized. Additionally, people with HIV (PWH) are five times as likely to develop cHL, and cHL in PWH is nearly exclusively EBV-associated. However, there are limited published molecular characterizations of cHL arising in PWH (HIV+ cHL). This gap is particularly impactful in the Global South where cancer mortality and HIV prevalence are high. In this study, we evaluated the whole exome, transcriptome, and T-cell receptor repertoire of an HIV-inclusive cohort of cHL patients from Malawi. HIV+ cHL had increased tumor mutational burden compared to cHL in people without HIV (HIV- cHL). EBV+/HIV- tumors exhibited a distinct transcriptional profile compared to EBV-/HIV- and EBV+/HIV+. Additionally, both EBV and HIV were associated with cellular composition changes within the tumor microenvironment, including increases in memory B cells and CD8+ T cells compared to EBV- and HIV- cHL. T-cell receptor clonality was increased in EBV+ cHL, with trend towards further increase in clonality in HIV+. Through a multiomic approach of a well-characterized, HIV-inclusive cHL cohort from one of the most resource-limited countries in the world, we were able to recapitulate known, and identify novel molecular differences by HIV and EBV status.