An immunogenic and oncogenic feature-based classification for chemotherapy plus PD-1 blockade in advanced esophageal squamous cell carcinoma.
Cancer Cell
; 41(5): 919-932.e5, 2023 05 08.
Article
in En
| MEDLINE
| ID: mdl-37059106
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Esophageal Neoplasms
/
Esophageal Squamous Cell Carcinoma
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2023
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA