Abstract 2038: Epstein-Barr virus shapes the tumor microenvironment in classical Hodgkin lymphoma

Abstract

Abstract The histopathologic appearance of classical Hodgkin lymphoma (cHL) is characterized by rare multinucleated malignant Hodgkin Reed-Sternberg (HRS) cells within a rich inflammatory tumor microenvironment (TME). A subset of cHL cases are associated with Epstein-Barr virus (EBV) infection, which is considered to play a part in cHL pathogenesis. Since EBV+ and EBV- cHL exhibit differing mechanisms of pathogenesis, we hypothesized that the composition and spatial architecture of the TME in EBV-associated cHL differs from that of EBV- cHL, with implications for stratifying patients for specific treatment regimens based on EBV positivity. Here, we designed a multimodal approach using spatially resolved multiplexed protein profiling, flow cytometry, immunohistochemistry, and transcriptomics to profile EBV positive and EBV negative cHL tumors. We measured over 27 million single cells and 1,000 unique proteomic cell states derived using 29 proteins in addition to the transcriptome in 43 patient tumors. We uncovered significant differences between EBV+ and EBV- cHL in relative abundance of specific immune cell types, immune activation state, and spatial organization of the HRS cell neighborhoods. We present a multidimensional characterization of cHL in relation to EBV with implications for therapeutic stratification of patients with virus-associated cHL. Citation Format: Maryam Pourmaleki, Caitlin J. Jones, Sabrina D. Mellinghoff, Brian Greenstein, Priyadarshini Kumar, Mikhail Roshal, Travis J. Hollmann, Nicholas D. Socci, Ahmet Dogan, Ingo K. Mellinghoff. Epstein-Barr virus shapes the tumor microenvironment in classical Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2038.