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

Abstract

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-γ 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-γ). Combined PD-1 ⁺ and Tim-3 ⁺ inhibition had a synergistic effect on IFN-γ 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.

Electronic supplementary material

The online version of this article (10.1186/s12935-017-0489-4) contains supplementary material, which is available to authorized users.