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Tumor-Infiltrating T Cells Concurrently Overexpress CD200R with Immune Checkpoints PD-1, CTLA-4, and TIM-3 in Non-Small-Cell Lung Cancer
Pathobiology ( IF 5 ) Pub Date : 2020-12-15 , DOI: 10.1159/000511557
Yinghan Su 1, 2 , Shota Yamazaki 1, 2 , Ryo Morisue 2, 3 , Jun Suzuki 2, 4 , Toshiaki Yoshikawa 5 , Tetsuya Nakatsura 5 , Masahiro Tsuboi 4 , Atsushi Ochiai 1, 6 , Genichiro Ishii 7, 8, 9
Affiliation  

INTRODUCTION CD200R has been reported to be the receptor for the immune checkpoint molecule CD200 and can transduce immune-suppressive signals. In this study, we mainly focused on the expression level of CD200R in T cells in pulmonary artery (PA) blood and non-small-cell lung cancer (NSCLC) tumor tissue. METHODS Immune cells were isolated from dissected tumor samples and PA blood of NSCLC patients and analyzed with multiparameter flow cytometry. The co-expression of CD200R with other immune checkpoints, including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), was also investigated. RESULTS CD200R expression was observed on the surface of approximately 75% of T cells among tumor-infiltrating leukocytes (TILs). Compared to T cells extracted from TILs, only 55% of T cells extracted from PA blood exhibited CD200R expression. Moreover, with higher expression of CD200R, the expression of other immune checkpoints, including PD-1, CTLA-4, and TIM-3, was also increased in tumor-infiltrating T cells compared to T cells in PA blood. CONCLUSIONS Our results showed that those tumors were dominated by T cells expressing CD200R together with other checkpoints, which suggests a phenotypic change after T cell infiltration into the tumor, such as T cell exhaustion.

中文翻译:

在非小细胞肺癌中,肿瘤浸润性 T 细胞同时过表达 CD200R 与免疫检查点 PD-1、CTLA-4 和 TIM-3

引言 据报道,CD200R 是免疫检查点分子 CD200 的受体,可以转导免疫抑制信号。在本研究中,我们主要关注肺动脉 (PA) 血液和非小细胞肺癌 (NSCLC) 肿瘤组织中 T 细胞中 CD200R 的表达水平。方法从NSCLC患者解剖的肿瘤样本和PA血液中分离免疫细胞,并用多参数流式细胞术进行分析。CD200R 与其他免疫检查点的共表达,包括程序性细胞死亡蛋白 1 (PD-1)、细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 和 T 细胞免疫球蛋白和含粘蛋白结构域的蛋白 3 (TIM) -3),也进行了调查。结果 在肿瘤浸润性白细胞 (TIL) 中大约 75% 的 T 细胞表面观察到 CD200R 表达。与从 TIL 中提取的 T 细胞相比,从 PA 血液中提取的 T 细胞中只有 55% 表现出 CD200R 表达。此外,随着 CD200R 的更高表达,与 PA 血液中的 T 细胞相比,其他免疫检查点(包括 PD-1、CTLA-4 和 TIM-3)在肿瘤浸润性 T 细胞中的表达也增加。结论 我们的结果表明,这些肿瘤以表达 CD200R 的 T 细胞和其他检查点为主,这表明 T 细胞浸润到肿瘤中后发生了表型变化,例如 T 细胞耗竭。
更新日期:2020-12-15
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