期刊
CANCER CELL INTERNATIONAL
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12935-017-0489-4
关键词
T lymphocytes; CD4(+) T-cells; Gastric cancer; IFN-gamma staining assay; Dysfunction
类别
资金
- National Key Technology RD Program [2015BAI12B12]
- National Clinical Research Center for Cancer, National Natural Science Foundation of China [81502648]
- Henan Medical Science and Technique Foundation [201401016]
- Zhengzhou Medical Science and Technique Foundation [153PKJGG061]
- Henan Students Studying Abroad Research Foundation [2015-5]
- Henan Provincial Scientific and technological project [162102310046]
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.
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