Intratumoral CD103⁺CD4⁺ T cell infiltration defines immunoevasive contexture and poor clinical outcomes in gastric cancer patients.

ABSTRACT: Our previous study has identified intratumoral CD103⁺CD8⁺ T cells as a favorable prognostic factor in gastric cancer. However, the significance of CD103⁺CD4⁺ T cells in gastric cancer hasn't yet been elucidated. Here, we aimed to investigate the clinical significance and phenotype characteristics of intratumoral CD103⁺CD4⁺ T cells in gastric cancer. In our study, 469 formalin-fixed and paraffin-embedded samples and 24 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital were included. We manifested that intratumoral CD103⁺CD4⁺ T cells in gastric cancer predicted poor overall survival and inferior responsiveness to fluorouracil-based ACT. The density and phenotypic characteristics of CD103⁺CD4⁺ T cells in gastric cancer were detected by immunohistochemistry and flow cytometry, which showed that CD103⁺CD4⁺ T cells exhibited an immunosuppressive phenotype and higher retention capacity in tumor tissues. Furthermore, increased CD103⁺CD4⁺ T cells contributed to CD8⁺T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Overall, this study revealed that intratumoral CD103⁺CD4⁺T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT. Therefore, we recommended that CD103⁺CD4⁺ T cells might be a potential immunotherapeutic target for gastric cancer.

SUBMITTER: Gu Y 

PROVIDER: S-EPMC7714530 | biostudies-literature |

REPOSITORIES: biostudies-literature