Intratumoral CD103(+)CD4(+) T cell infiltration defines immunoevasive contexture and poor clinical outcomes in gastric cancer patients.
Intratumoral CD103(+)CD4(+) T cell infiltration defines immunoevasive contexture and poor clinical outcomes in gastric cancer patients.
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瘤内 CD103 CD4 T 细胞浸润定义了胃癌患者的免疫逃避环境和不良临床结果
DOI：
10.1080/2162402x.2020.1844402
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发表时间：
2020-11-22
期刊：
影响因子：
7.2
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Gu Y;Chen Y;Jin K;Cao Y;Liu X;Lv K;He X;Lin C;Liu H;Li H;He H;Qin J;Li R;Zhang H;Zhang W
我们先前的研究已经确定肿瘤内CD 103 + CD 8 + T细胞是胃癌的有利预后因素。但CD 103 + CD 4 + T细胞在胃癌中的意义尚不清楚。本研究旨在探讨胃癌组织中CD 103 + CD 4 + T细胞的表型特征及其临床意义。本研究包括469例福尔马林固定石蜡包埋的胃癌标本和24例新鲜胃癌组织标本。我们发现，胃癌中肿瘤内CD 103 + CD 4 + T细胞预测总体生存率较差，对氟尿嘧啶为基础的ACT的反应性较差。采用免疫组化和流式细胞术检测胃癌组织中CD 103 + CD 4 + T细胞的密度和表型特征，结果显示CD 103 + CD 4 + T细胞具有免疫抑制表型，在肿瘤组织中具有较高的滞留能力。此外，胃癌中CD 103 + CD 4 + T细胞增加导致CD 8 +T细胞功能障碍，颗粒酶B（GZMB）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和穿孔素（PRF-1）表达降低。总体而言，这项研究表明，肿瘤内CD 103 + CD 4 +T细胞浸润定义免疫逃避结构，并预测预后不良和对氟尿嘧啶为基础的ACT的反应性较差。因此，我们认为CD 103 + CD 4 + T细胞可能是胃癌潜在的免疫靶点。
Our previous study has identified intratumoral CD103+CD8+ T cells as a favorable prognostic factor in gastric cancer. However, the significance of CD103+CD4+ T cells in gastric cancer hasn’t yet been elucidated. Here, we aimed to investigate the clinical significance and phenotype characteristics of intratumoral CD103+CD4+ T cells in gastric cancer. In our study, 469 formalin-fixed and paraffin-embedded samples and 24 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital were included. We manifested that intratumoral CD103+CD4+ T cells in gastric cancer predicted poor overall survival and inferior responsiveness to fluorouracil-based ACT. The density and phenotypic characteristics of CD103+CD4+ T cells in gastric cancer were detected by immunohistochemistry and flow cytometry, which showed that CD103+CD4+ T cells exhibited an immunosuppressive phenotype and higher retention capacity in tumor tissues. Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Overall, this study revealed that intratumoral CD103+CD4+T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT. Therefore, we recommended that CD103+CD4+ T cells might be a potential immunotherapeutic target for gastric cancer.