Open AccessTumor-Infiltrating T Cells Concurrently Overexpress CD200R with Immune Checkpoints PD-1, CTLA-4, and TIM-3 in Non-Small-Cell Lung Cancer
Author(s) -
Yinghan Su,
Shota Yamazaki,
Ryo Morisue,
Jun Suzuki,
Toshiaki Yoshikawa,
Tetsuya Nakatsura,
Masahiro Tsuboi,
Atsushi Ochiai
Publication year - 2020
Publication title -
pathobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.941
H-Index - 53
eISSN - 1423-0291
pISSN - 1015-2008
DOI - 10.1159/000511557
Subject(s) - cytotoxic t cell , immune system , cancer research , antibody , t cell , biology , ctla 4 , immune checkpoint , lymphocyte , immunology , immunotherapy , in vitro , biochemistry
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.