Analysis of immunotherapeutic response-related signatures in esophageal squamous-cell carcinoma

Bohao Zheng; Jie Li; Mengdi Zhang; Pengju Zhang; Weiwei Deng; Yang Pu

doi:10.3389/fimmu.2023.1117658

Analysis of immunotherapeutic response-related signatures in esophageal squamous-cell carcinoma

Front Immunol. 2023 Feb 2:14:1117658. doi: 10.3389/fimmu.2023.1117658. eCollection 2023.

Authors

Bohao Zheng¹, Jie Li¹, Mengdi Zhang¹, Pengju Zhang¹, Weiwei Deng¹, Yang Pu¹

Affiliation

¹ State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common and lethal malignant diseases. Immunotherapy has been widely studied and has exhibited potential in ESCC treatment. However, there are only a portion of ESCC patients have benefited from immunotherapy. We herein identified immunotherapeutic response-related signatures (IRRS) and evaluated their performance in ESCC prognosis and immunotherapeutic responsiveness.

Methods: We constructed an IRRS using the gene expression data of 274 ESCC patients based on y -30significantly differentially expressed genes, which were compared responders and non-responders from various patient cohorts treated with immunotherapy. Survival analysis was performed in both the GSE53625 and TCGA-ESCC cohorts. We also explored the differences in the tumor microenvironment between the high-IRRS and low-IRRS score groups using single-cell data as a reference. Three immunotherapy cohorts were used to verify the value of the IRRS in predicting immunotherapy response.

Results: Twelve immunotherapy-related genes were selected to construct a signature score and were validated as independent prognostic predictors for patients with ESCC. Patients with high IRRS scores exhibited an immunosuppressive phenotype. Therefore, patients with low IRRS scores may benefit from immunotherapy.

Conclusions: IRRS score is a biomarker for immunotherapy response and prognosis of ESCC.

Keywords: esophageal squamous-cell carcinoma (ESCC); immunotherapeutic responsiveness; immunotherapy; prognosis; single-cell RNA sequencing; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma* / pathology
Humans
Immunotherapy
Prognosis
Tumor Microenvironment

Substances

Biomarkers, Tumor

Grants and funding

This work was supported by National Science and Technology Major Project (2021YFC2502000), Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0012), National Natural Science Foundation of China (82273163, 32100554).