Correlation between Tumor Microenvironment and Immune Subtypes Based on CD8 T Cells Enhancing Personalized Therapy of Gastric Cancer

Abstract

Background. Immunotherapy is a promising therapy for metastatic gastric cancer (GC) patients. However, the component of tumor microenvironment (TME) is a pivotal factor hindering immunotherapy outcome. CD8 T cells suppress tumor progression. This study developed an immune subtyping system and a prognostic model for guiding personalized therapy of GC patients. Methods. Marker genes related to CD8 T cells were identified by weighted correlation network analysis (WGCNA). Consensus clustering was used to develop immune subtypes. Univariate Cox regression analysis was performed to screen prognostic genes. Functional analysis (KEGG and GO annotation) and gene set enrichment analysis were applied. Results. Based on marker genes related to CD8 T cells, we identified three immune subtypes (IC1, IC2, and IC3) with distinct prognosis and differential TME. In IC3, CD8 T cell function was impaired by high activation of CXCR4/CXCL12 axis, and impaired T cell function predicted high response to immune checkpoint blockade. IC1 was sensitive to chemotherapeutic drugs but showed low response to immunotherapy. We also developed an 8-gene prognostic signature with robust performance to stratify GC patients into high-risk and low-risk groups. Conclusions. This study identified three immune subtypes and a prognostic signature, and both were effective in direct personalized therapy for GC patients. The correlation between TME and immunotherapy was further characterized from a new perspective.