PD-1+和Tim-3+ CD8+ T细胞数量增加参与胃癌的免疫逃逸。
An increased number of PD-1+ and Tim-3+ CD8+ T cells is involved in immune evasion in gastric cancer.
作者信息
Takano Shuichi, Saito Hiroaki, Ikeguchi Masahide
机构信息
Division of Surgical Oncology, Department of Surgery, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
出版信息
Surg Today. 2016 Nov;46(11):1341-7. doi: 10.1007/s00595-016-1305-9. Epub 2016 Jan 22.
PURPOSE
Co-signaling molecules play an important role in T cells. This study was designed to investigate PD-1 and Tim-3 expression on T cells and the relationships between PD-1 and Tim-3 expression and immune evasion in patients with gastric cancer.
METHODS
Using multicolor flow cytometry, we analyzed PD-1 and Tim-3 expression on CD8+ T cells obtained from peripheral blood mononuclear cells (PBMCs) and gastric cancer tissue.
RESULTS
Significantly more PD-1+ and Tim-3+ CD8+ T cells in peripheral blood were found in gastric cancer patients than in healthy controls. PD-1+ CD8+ T cells were significantly correlated with Tim-3+ CD8+ T cells in peripheral blood from the gastric cancer patients (r = 0.29, p = 0.036). Furthermore, significantly greater numbers of PD-1+ and Tim-3+ CD8+ T cells were seen in the gastric cancer tissue samples than in the PBMCs. CD8+ T cells positive for both PD-1 and Tim-3 produced significantly less IFN-gamma than cells negative for both and cells positive for PD-1 and negative for Tim-3.
CONCLUSION
An increased number of PD-1+ and Tim-3+ CD8+ T cells is closely related to impaired function of CD8+ T cells in gastric cancer patients.
目的
共信号分子在T细胞中发挥重要作用。本研究旨在探讨胃癌患者T细胞上程序性死亡受体1（PD-1）和T细胞免疫球蛋白黏蛋白分子3（Tim-3）的表达情况，以及PD-1和Tim-3表达与免疫逃逸之间的关系。
方法
采用多色流式细胞术，分析从外周血单个核细胞（PBMC）和胃癌组织中获取的CD8⁺T细胞上PD-1和Tim-3的表达。
结果
与健康对照相比，胃癌患者外周血中PD-1⁺和Tim-3⁺CD8⁺T细胞显著增多。胃癌患者外周血中PD-1⁺CD8⁺T细胞与Tim-3⁺CD8⁺T细胞显著相关（r = 0.29，p = 0.036）。此外，胃癌组织样本中PD-1⁺和Tim-3⁺CD8⁺T细胞数量显著多于PBMC中的数量。同时表达PD-1和Tim-3的CD8⁺T细胞产生的γ干扰素显著少于双阴性细胞以及PD-1阳性、Tim-3阴性的细胞。
结论
胃癌患者中PD-1⁺和Tim-3⁺CD8⁺T细胞数量增加与CD8⁺T细胞功能受损密切相关。
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