期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 9, 页码 2325-2337出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20180577
关键词
-
资金
- Dutch Cancer Foundation [2013-6142]
Most T cell-based immunotherapies of cancer depend on intact antigen presentation by HLA class I molecules (HLA-I). However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8(+) T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans. These HLA-A*02:01 presented peptides do not derive from the mutanome of cancers, but are of self origin and therefore constitute universal neoantigens. Indeed, CD8(+) T cells specific for the leader peptide of the ubiquitously expressed LRP AP1 protein recognized TAP-deficient, HLA-I-low lymphomas, melanomas, and renal and colon carcinomas, but not healthy counterparts. In contrast to personalized mutanome-targeted therapies, these conserved neoantigens and their cognate receptors can be exploited for immune-escaped cancers across diverse histological origins.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据