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

Oncoimmunology. 2020 Nov 22;9(1):1844402. doi: 10.1080/2162402X.2020.1844402.

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.

Keywords: CD103+CD4+ T cell; Gastric cancer; adjuvant therapy; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Fluorouracil / therapeutic use
  • Humans
  • Prognosis
  • Stomach Neoplasms* / therapy

Substances

  • Fluorouracil

Grants and funding

This study was funded by grants from National Natural Science Foundation of China (81671628, 81871306, 81871926, 81871930, 81902402, 81902901, 81972219), Shanghai Municipal Natural Science Foundation (18ZR1432900), and Shanghai Sailing Program (17YF1402200, 18YF1404600, 19YF1407500). All these study sponsors have no roles in the study design, in the collection, analysis and interpretation of data.