免疫疗法
免疫系统
生物
免疫检查点
细胞毒性T细胞
CD8型
免疫学
癌症免疫疗法
封锁
抗原
癌症研究
T细胞
癌症
体外
受体
生物化学
遗传学
作者
Adrienne Luoma,Shengbao Suo,Yifan Wang,Lauren Gunasti,Caroline Porter,Nancy H. Nabilsi,Jenny Tadros,Andrew Ferretti,Sida Liao,Cagan Gurer,Yu‐Hui Chen,Shana Criscitiello,Cora A. Ricker,Danielle Dionne,Orit Rozenblatt–Rosen,Ravindra Uppaluri,Robert I. Haddad,Orr Ashenberg,Aviv Regev,Eliezer M. Van Allen,Gavin MacBeath,Jonathan D. Schoenfeld,Kai W. Wucherpfennig
出处
期刊:Cell
[Elsevier]
日期:2022-07-07
卷期号:185 (16): 2918-2935.e29
被引量:173
标识
DOI:10.1016/j.cell.2022.06.018
摘要
Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here, we characterized early kinetics in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs, which were already active prior to therapy, supporting the capacity for rapid response. Systematic target discovery revealed that treatment-expanded tumor T cell clones in responding patients recognized several self-antigens, including the cancer-specific antigen MAGEA1. Treatment also induced a systemic immune response characterized by expansion of activated T cells enriched for tumor-infiltrating T cell clonotypes, including both pre-existing and emergent clonotypes undetectable prior to therapy. The frequency of activated blood CD8 T cells, notably pre-treatment PD-1-positive KLRG1-negative T cells, was strongly associated with intra-tumoral pathological response. These results demonstrate how neoadjuvant checkpoint blockade induces local and systemic tumor immunity.
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