Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing 400038, People's Republic of China.
Cancer Immunol Immunother. 2012 Nov;61(11):2183-92. doi: 10.1007/s00262-012-1277-6. Epub 2012 May 22.
CD8(+)Foxp3(+) T lymphocytes have been detected in tumors. However, the distribution, phenotypic features, and regulation of these cells in gastric cancer remain unknown.
The levels of CD8(+)Foxp3(+) T lymphocytes in the peripheral blood, tumor-draining lymph nodes, non-tumor 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.
The frequency of CD8(+)Foxp3(+) T lymphocytes in tumor tissues was significantly higher than that in non-tumor 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-β1 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.
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.
已经在肿瘤中检测到 CD8(+)Foxp3(+)T 淋巴细胞。然而，胃癌中这些细胞的分布、表型特征和调节仍不清楚。
通过流式细胞术检测胃癌患者外周血、肿瘤引流淋巴结、非肿瘤组织和肿瘤组织中 CD8(+)Foxp3(+)T 淋巴细胞的水平。体外研究 Foxp3 在 CD8(+)Foxp3(-)T 细胞中的诱导情况。分析 CD8(+)Foxp3(+)T 淋巴细胞对 CD4(+)T 细胞增殖和 IFN-γ 产生的抑制功能。评估 CD8(+)Foxp3(+)T 淋巴细胞的百分比与肿瘤分期的相关性。
肿瘤组织中 CD8(+)Foxp3(+)T 淋巴细胞的频率明显高于非肿瘤组织，肿瘤引流淋巴结与外周血相比也观察到类似结果。大多数肿瘤内 CD8(+)Foxp3(+)T 淋巴细胞为活化效应细胞（CD45RA(-)CD27(-)）。TGF-β1 水平与肿瘤组织中 CD8(+)Foxp3(+)T 淋巴细胞的频率呈正相关，体外 TGF-β1 可以剂量依赖性诱导 CD8(+)Foxp3(+)T 淋巴细胞的产生。此外，肿瘤内 CD8(+)Foxp3(+)T 淋巴细胞抑制 CD4(+)T 细胞的增殖和 IFN-γ 产生。最后，肿瘤内 CD8(+)Foxp3(+)T 淋巴细胞随着肿瘤进展（TNM 分期）而显著增加。
我们的数据表明，肿瘤内 CD8(+)Foxp3(+)T 淋巴细胞的增加与肿瘤分期有关，并可能影响 CD4(+)T 细胞功能，这可能为开发针对胃癌的新型免疫治疗方案提供思路。
