Increased tumor-infiltrating CD8+Foxp3+ T lymphocytes are associated with tumor progression in human gastric cancer

摘要

Background CD8+Foxp3+ T lymphocytes have been detected in tumors. However, the distribution, phenotypic features, and regulation of these cells in gastric cancer remain unknown. Methods The levels of CD8+Foxp3+ T lymphocytes in the peripheral blood, tumor-draining lymph nodes, nontumor tissues, and tumor tissues of patients with gastric cancer were detected by flow cytometry. Foxp3 induction in CD8 +Foxp3- T cells was investigated in vitro. The suppressive function of CD8+Foxp3+ T lymphocytes was analyzed by their effect on CD4+ T-cell proliferation and IFN-γ production. The percentages of CD8+Foxp3+ T lymphocytes were evaluated for the association with tumor stage. Results The frequency of CD8 +Foxp3+ T lymphocytes in tumor tissues was significantly higher than that in nontumor tissues, and similar results were also observed in tumor-draining lymph nodes compared with peripheral blood. Most intratumoral CD8+Foxp3+ T lymphocytes were activated effector cells (CD45RA-CD27-). TGF-β1 levels were positively correlated with the frequency of CD8+Foxp3+ T lymphocytes in tumor tissues, and in vitro TGF-b1 could induce the generation of CD8+Foxp3+ T lymphocytes in a dose-dependent manner. Furthermore, intratumoral CD8 +Foxp3+ T lymphocytes suppressed the proliferation and IFN-γ production of CD4+ T cells. Finally, intratumoral CD8+Foxp3+ T lymphocytes were significantly increased with tumor progression in terms of tumor-node-metastasis (TNM) stage. Conclusions Our data have shown that increased intratumoral CD8+Foxp3+ T lymphocytes are associated with tumor stage and potentially influence CD4+ T-cell functions, which may provide insights for developing novel immunotherapy protocols against gastric cancer.