癌症研究
封锁
肿瘤科
癌症
免疫原性
食管癌
外显子组测序
化疗
免疫疗法
生物
医学
内科学
突变
免疫学
免疫系统
基因
遗传学
受体
作者
Yan‐Xing Chen,Zi‐Xian Wang,Ying Jin,Qi Zhao,Zexian Liu,Zhixiang Zuo,Huai-Qiang Ju,Chengxu Cui,Jun Yao,Yanqiao Zhang,Mengxia Li,Jifeng Feng,Lin Tian,Xiaojun Xia,Hui Feng,Sheng Yao,Fenghua Wang,Yuhong Li,Rui Wang,Rui‐Hua Xu
出处
期刊:Cancer Cell
[Elsevier]
日期:2023-05-01
卷期号:41 (5): 919-932.e5
被引量:8
标识
DOI:10.1016/j.ccell.2023.03.016
摘要
Although chemotherapy plus PD-1 blockade (chemo+anti-PD-1) has become the standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), reliable biomarkers for this regimen are lacking. Here we perform whole-exome sequencing on tumor samples from 486 patients of the JUPITER-06 study and develop a copy number alteration-corrected tumor mutational burden that depicts immunogenicity more precisely and predicts chemo+anti-PD-1 efficacy. We identify several other favorable immunogenic features (e.g., HLA-I/II diversity) and risk oncogenic alterations (e.g., PIK3CA and TET2 mutation) associated with chemo+anti-PD-1 efficacy. An esophageal cancer genome-based immuno-oncology classification (EGIC) scheme incorporating these immunogenic features and oncogenic alterations is established. Chemo+anti-PD-1 achieves significant survival improvements in EGIC1 (immunogenic feature-favorable and oncogenic alteration-negative) and EGIC2 (either immunogenic feature-favorable or oncogenic alteration-negative) subgroups, but not the EGIC3 subgroup (immunogenic feature-unfavorable and oncogenic alteration-positive). Thus, EGIC may guide future individualized treatment strategies and inform mechanistic biomarker research for chemo+anti-PD-1 treatment in patients with advanced ESCC.
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