Poor clinical outcomes and immunoevasive contexture in CXCL13+CD8+T cells enriched gastric cancer patients

As an adverse survival prognosticator, chemokine (C-X-C motif) ligand 13 (CXCL13) has been studied in several types of malignancies. The secretion and physiological roles of CXCL13 in follicular helper T cells (T-FH) cells have been well described, while the clinical significance of CD8(+) tumor-infiltrating lymphocytes (TILs)-associated CXCL13 remains unknown. This study aims to investigate the clinical significance of CXCL13(+)CD8(+) T cells in survival and chemotherapeutic responsiveness prediction in gastric cancer. In this study, 440 patients enrolled from Zhongshan Hospital with tumor microarray (TMA) specimens were randomly divided into testing set (n = 220) and validation set (n = 220) for analysis. CXCL13(+)CD8(+) T cells were detected by multicolor immunohistochemistry. Fresh tumor tissue samples from another 60 gastric cancer patients were collected to detect CXCL13(+)CD8(+) T cells functional status by flow cytometry (FCM). We found that high intratumoral CXCL13(+)CD8(+) T cells infiltration predicted poor overall survival and inferior chemotherapeutic responsiveness in gastric cancer. CXCL13(+)CD8(+)T cells were associated with immunoevasive contexture with increased regulatory T (T-reg) cells and dysfunctional cytotoxic T lymphocytes (CTLs). Moreover, the combinational analysis of CXCL13(+)CD8(+) T cells and CD8(+) T cells infiltration stratified patients into distinct risk groups with different clinical outcomes and chemotherapeutic responsiveness. Conclusively, intratumoral CXCL13(+)CD8(+) T cells infiltration could be an independent prognostic and predictive marker for gastric cancer patients. CXCL13(+)CD8(+) T cells represented an exhausted CD8(+) T cell subset, and might be a potential immunotherapeutic target in gastric cancer.

Automated summary

High intra-tumoral infiltration of CXCL13(+)CD8(+) T cells predicted poor overall survival and inferior chemotherapeutic responsiveness in gastric cancer. These cells were associated with an immune-evasive contexture characterized by increased regulatory T cells and dysfunctional cytotoxic T lymphocytes. The combinatorial analysis of CXCL13(+)CD8(+) T cell and CD8(+) T cell infiltration stratified patients into distinct risk groups with varying clinical outcomes and responsiveness to chemotherapy. This suggests that intra-tumoral CXCL13(+)CD8(+) T cell infiltration could serve as an independent prognostic and predictive marker for gastric cancer patients.