Tumor-infiltrating CD4+ T cells in patients with gastric cancer

Background: T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4(+) T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Materials and methods: Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-gamma staining assay is conducted. Statistical analysis is performed to show significance. Results: The results showed that the percentage of CD4(+) T-cells among CD3(+) cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4(+) CD25(high) CD127(low) regulatory T-cells (Tregs), PD-1(+), Tim-3(+), and PD-1(+) Tim-3(+) cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1(+) and Tim-3(+) were effective in restoring tumor infiltrating T-cells' production of interferon-gamma (IFN-gamma). Combined PD-1(+) and Tim-3(+) inhibition had a synergistic effect on IFN-gamma secretion by CD4(+) T-cells. Conclusion: The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided.