Abstract P12: Bystander activation drives CD8+ T cells response in Lymphoma-associated Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a fulminant disease characterized by overwhelming inflammatory response leading to dismal outcomes. Amongst patients with secondary HLH, lymphoma-associated HLH has the worst outcome. While aberrant activation of cytotoxic CD8+ T cells is the central attributor in HLH, how these cells are broadly activated remains unclear. In this study, we aim to uncover the mechanisms and pathways involved in the activation of these T cells. Using high-plex cytometry, single-cell RNA and T cell receptor sequencing to profile peripheral CD8+ T cells from lymphoma patients with HLH, our findings revealed that these highly activated CD8+ T cells from HLH patients were driven by IL-15-mediated bystander activation. These bystander-activated T cells are also likely to have caused extensive organ damage in HLH patients. Insights from this study indicated that targeting the IL-15 pathway could be a potential therapeutic avenue to reduce the severity of HLH.