Dysfunctional role of elevated TIGIT expression on T cells in oral squamous cell carcinoma patients
Dysfunctional role of elevated TIGIT expression on T cells in oral squamous cell carcinoma patients
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口腔鳞状细胞癌患者 T 细胞 TIGIT 表达升高的功能失调作用
DOI：
10.1111/odi.13703
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发表时间：
2020-11-19
期刊：
影响因子：
3.8
通讯作者：
Wang, Zhi
中科院分区：
文献类型：
--
作者：
Liu, Xiangqi;Li, Qunxing;Wang, Zhi
目的探讨口腔鳞状细胞癌（OSCC）患者外周血单个核细胞（PBMC）和肿瘤浸润淋巴细胞（TIL）中T细胞免疫受体（TIGIT）的表达及其在OSCC发生发展中的作用。采用卡方检验分析TIGIT表达与临床病理特征的相关性。结果TIGIT高表达于PBMC和TIL的T细胞表面，TIGIT（+）T细胞的表型和功能均高于对照组。TIGIT在CD 4（+）T细胞（19.0%）和CD 8（+）T细胞（35.9%）上的高表达也与较高的T分期和淋巴结浸润相关。此外，从OSCC患者分选的TIGIT（+）CD 4（+）和TIGIT（+）CD 8（+）T细胞显示出功能失调的表型（低细胞增殖和IL-2、TNF-α和IFN-γ的低分泌），并且TIGIT（+）CD 4（+）T细胞表现出抑制功能（Foxp 3的高表达和高量的IL-10）。重要的是，TIGIT阻断可以增强OSCC患者CD 4（+）和CD 8（+）T细胞的增殖能力和有效的细胞因子（IL-2、TNF-α和IFN-γ）产生。
Objective This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC).Materials and Methods Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi-square test. Phenotypic and functional study of TIGIT(+) T cells were performed by flow cytometry.Results TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4(+) T cells (19.0%) and CD8(+) T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT(+)CD4(+) and TIGIT(+)CD8(+) T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-alpha and IFN-gamma), and TIGIT(+)CD4(+) T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-alpha, and IFN-gamma) of CD4(+) and CD8(+) T cells from OSCC patients in vitro.Conclusions TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.