CXCL9/10/11 as prognostic indicators for immunotherapy response in gastric cancer

Abstract

Objective: Gastric cancer remains a major cause of cancer related mortality and only a group of patients benefits from immune checkpoint inhibitors. This study aimed to evaluate the expression profiles, immune associations, prognostic value, and predictive potential for immunotherapy responsiveness of CXCL9, CXCL10, CXCL11, and CXCR3.

Materials and Methods: Gene expression levels of CXCL9, CXCL10, CXCL11, and CXCR3 in gastric tumor tissues and normal tissues were analyzed using GEPIA. Co-expression among CXCL9/10/11 were performed using cBioPortal. Correlations and immunotherapy prediction analyses were performed using TIMER3. Overall survival analyses were assessed using Kaplan-Meier Plotter.

Results: A significant increase in CXCL9, CXCL10, CXCL11, and CXCR3 expression was observed in gastric tumor tissues versus normal tissues with no stage-dependent differences. High expression of CXCL9, CXCL10, and CXCL11 were correlated with higher infiltration of CD8+ T cells, M1 macrophages, and lower infiltration of M2 macrophages and myeloid-derived suppressor cells. Increased expressions of IFNG, GZMB, TBX21, and STAT1 were positively correlated with CXCL9/10/11 expression. Patients with high CXCL9/10/11 expression demonstrated favorable overall survival and improved immunotherapy response.

Conclusion: CXCR3-CXCL9/10/11 axis is associated with an immune-inflamed phenotype, improved survival, and enhanced immunotherapy responsiveness in gastric cancer. These results indicate that CXCL9/10/11 may function as potential biomarkers of immunotherapy responsiveness.