[대학원 생명과학과 세미나 안내]
연사 : 최일규 교수(DGIST, 뉴바이올로지학과)
연제 : T cell immunity to Epstein-Barr virus:
from new paradigm to immunotherapeutic application
일시 : 2022년 10월 21일 (금) 오후 4시 30분
장소 : 하나과학관 A동 109호
초청교수 : 이헌상 교수
Abstract
Tumor-associated antigens (TAAs) comprise a large collection of non-mutated cellular antigens recognized by T cells in human and murine cancers. Their potential as immunotherapy targets has been explored for over two decades yet the genesis of TAA-specific T cells remains elusive. While tumor cells may be a major source of TAAs for T cell priming, several recent studies suggest that infection with some viruses including Epstein-Barr virus (EBV) can elicit cytotoxic T cell responses against some abnormally expressed cellular antigens that function as TAAs. However, the cellular and molecular basis of such responses remains undefined. Here, we show that expression of the EBV signaling protein LMP1 in B cells provokes T cell responses to multiple TAAs. LMP1 signaling leads to overexpression of many cellular antigens previously shown to be TAAs, their presentation on MHC-I and -II (mainly through the endogenous pathway) and the upregulation of costimulatory ligands CD70 and OX40 ligand, thereby inducing potent cytotoxic CD4+ and CD8+ T cell responses. These findings delineate a novel mechanism of infection-induced anti-tumor immunity. Furthermore, by ectopically expressing LMP1 in patient tumor B cells and thereby empowering them to prime T cells, we develop a general approach for rapid production of autologous cytotoxic CD4+ T cells against a broad array of endogenous tumor antigens, such as TAAs and neoantigens, for treating B cell malignancies. This work stresses the need to revisit classical concepts concerning viral and tumor immunity, which will be critical to fully understand the impact of common infections on human health and to improve the rational design of immune approaches for cancers.