An immunogenic and oncogenic feature-based classification for chemotherapy plus PD-1 blockade in advanced esophageal squamous cell carcinoma

作者：Chen, Yan-Xing; Wang, Zi-Xian; Jin, Ying; Zhao, Qi; Liu, Ze-Xia; Zuo, Zhi-Xiang; Ju, Huai-Qiang; Cui, Chengxu; Yao, Jun; Zhang, Yanqiao; Li, Mengxia; Feng, Jifeng; Tian, Lin; Xia, Xiao-Jun; Feng, Hui; Yao, Sheng; Wang, Feng-Hua; Li, Yu-Hong; Wang, Feng; Xu, Rui-Hua^*

来源：Cancer Cell, 2023, 41(5): 919-+.

DOI：10.1016/j.ccell.2023.03.016

• CHECKPOINT BLOCKADE
• 1ST-LINE TREATMENT
• COPY NUMBER
• CANCER
• PEMBROLIZUMAB
• MUTATIONS
• CISPLATIN
• NIVOLUMAB
• BIOMARKER
• PATTERNS

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 pre-cisely 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) sub-groups, 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.

• 单位
  中国医学科学院; 哈尔滨医科大学; 1; 中山大学