Distinct immune signatures for predicting the immunotherapy efficacy of esophageal squamous cell carcinoma or adenocarcinoma.

Abstract

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are distinct histological subtypes of esophageal cancer. The tumor microenvironment of each subtype significantly influences the efficacy of immunotherapy. However, the characteristics of the tumor microenvironments of both subtypes, as well as their specific impacts on immunotherapy outcomes, still require further elucidation. Through the integration of gene expression profiles from ESCC and EAC obtained from The Cancer Genome Atlas database, alongside tumor tissues derived from Chinese patients, we identified TNFSF10, CXCL10, IL17RB, and CSF2 as pivotal immune molecules with significant prognostic implications. Elevated expression levels of TNFSF10 correlated with adverse outcomes in individuals diagnosed with ESCC. In contrast to patients from other geographical regions, CXCL10, IL17RB, and CSF2 exhibited distinct prognostic implications in Chinese patients with esophageal cancer. The Cox risk scores derived from the molecules TNFSF10 and CXCL10 for ESCC and IL17RB and CSF2 for EAC were used to assess their predictive capacity for immunotherapy efficacy. The results indicate that patients with lower Cox risk scores demonstrated an enhanced response to immunotherapeutic interventions. This study revealed significant disparities in the expression and functionality of immune-related molecules between ESCC and EAC and highlighted the potential of Cox risk scores derived from immune-related molecules to predict the efficacy of immunotherapy in patients. The findings underscore the clinical relevance of these biomarkers and emphasize the necessity for developing ethnic-specific biomarkers to guide personalized immunotherapy strategies between ESCC and EAC.