CD8⁺ T Cell Infiltration Elicits Molecular Subtype-Biased Clinical Outcomes in Gastric Cancer Patients

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• CD8+ T cell infiltration is crucial for anti-tumor immunity.
• Its clinical significance in gastric cancer (GC) is not well-defined.
• Gastric cancer exhibits molecular heterogeneity with four subtypes: EBV-positive, MSI, CIN, and GS.

Purpose of the Study:

• To investigate the distribution, clinical relevance, and immune associations of CD8+ T cell infiltration within GC's molecular subtypes.
• To understand the prognostic and predictive value of CD8+ T cells in different GC molecular subtypes.

Main Methods:

• Analysis of TCGA (n=336) and Zhongshan Hospital (ZSHS, n=455) cohorts.
• Comparison of CD8+ T cell infiltration and immune features across TCGA molecular subtypes.
• Evaluation of prognostic and predictive significance of CD8+ T cells in the ZSHS cohort.

Main Results:

• Elevated CD8+ T cell infiltration observed in EBV-positive and MSI subtypes.
• High CD8+ T cell infiltration correlated with better overall survival in EBV-positive and CIN subtypes.
• Low CD8+ T cell infiltration predicted superior response to adjuvant chemotherapy in MSI patients.
• Distinct immune associations of CD8+ T cells were found across subtypes.

Conclusions:

• CD8+ T cell infiltration has subtype-specific prognostic and therapeutic significance in gastric cancer.
• It is beneficial in EBV-positive and CIN subtypes and predictive of chemotherapy response in MSI subtypes with low infiltration.
• These findings highlight the heterogeneous immunological landscape of gastric cancer.