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

Abstract

BackgroundT 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 methodsPatients 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.ResultsThe 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+ CD25high CD127low 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.ConclusionThe 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 materialThe online version of this article (10.1186/s12935-017-0489-4) contains supplementary material, which is available to authorized users.

Function of fibroblast growth factor 2 in gastric cancer occurrence and prognosis

“…M2 macrophages are hypothesized to promote tumor growth, infiltration and metastasis, and their degree of infiltration is negatively correlated with the prognosis of patients (39,40). cd4 + T cells are important for the protection against cancer (41). in the present study, patients in the FGF2-l group had more dendritic cells, cd4 + memory activated T cells, fewer M2 cells, and a higher survival rate.…”

Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer

“…The study of Yuan et al[ 79 ] revealed that gastric cancers present an increased percentage of CD4 + T lymphocytes and lower CD8 + T cells (with an increased CD4 + /CD8 + ratio) compared to blood and, further, to paraneoplastic tissue. In addition, the number of TILs of effector and memory T cell type is significantly higher than in the case of circulating T cells.…”

“…As we have already mentioned, the involvement of Tregs in antitumor immunity is controversial, and their role may differ according to the type of cancer[ 80 , 81 ]. These authors considered CD4 + CD25 high CD127 low as being the most specific marker to define the Treg population, with the percentage of these cells being increased among TILs, demonstrating the accumulation of immunosuppressive Tregs at the site of a gastric tumor[ 79 ]. Recent studies show that the coexpression of PD-1 + and Tim-3 + define the most hypo-functional T lymphocytes[ 32 , 82 ].…”

“…The percentage of these cells among TILs was significantly increased in gastric tumors, especially in patients with advanced stages, suggesting that they may be implicated in a tumor immune escape phenomenon and that TILs in gastric cancer show T cell dysfunction. The combined blockade of these molecules seemed to have a synergistic effect on IFNγ production and, therefore, may provide new promising immune modulating strategies[ 79 ].…”

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

“…In line with our result, it has been demonstrated recently that Tregs with suppressive activity were upregulated on tumor-infiltrating T cells from patients with gastric cancer compared with their expressions on corresponding peripheral blood. 28 Furthermore, it has been reported that an increased number of peripheral blood CD8 + T cells can predict a better response to RT in patients with cancer and suggested that antitumor immunity may play Figure 3 Phenotyping and functional characterization of patient's T cells from peripheral blood using flow cytometry. (A) Dot blots represent CD4 + and CD8 + subsets (gated on CD3 + T cells) at disease progression, resolution and re-progression.…”