CD147 regulates antitumor CD8+ T-cell responses to facilitate tumor-immune escape

Chen，Yatong1; Xu，Jing1,2; Wu，Xiaodong1,3; Yao，Hui1,4; Yan，Zhou1; Guo，Ting1; Wang，Wenjing1; Wang，Peixiao1,5; Li，Yu1; Yang，Xiangmin1; Li，Hao1; Bian，Huijie1; Chen，Zhi Nan1

2020

10.1038/s41423-020-00570-y

Cellular & Molecular Immunology   影响因子和分区

1672-7681

2042-0226

Negative regulation of antitumor T-cell-immune responses facilitates tumor-immune escape. Here, we show that deletion of CD147, a type I transmembrane molecule, in T cells, strongly limits in vivo tumor growth of mouse melanoma and lung cancer in a CD8 T-cell-dependent manner. In mouse tumor models, CD147 expression was upregulated on CD8 tumor-infiltrating lymphocytes (TILs), and CD147 was coexpressed with two immune-checkpoint molecules, Tim-3 and PD-1. Mining publicly available gene-profiling data for CD8 TILs in tumor biopsies from metastatic melanoma patients showed a higher level of CD147 expression in exhausted CD8 TILs than in other subsets of CD8 TILs, along with expression of PD-1 and TIM-3. Additionally, CD147 deletion increased the abundance of TILs, cytotoxic effector function of CD8 T cells, and frequency of PD-1 CD8 TILs, and partly reversed the dysfunctional status of PD-1Tim-3CD8 TILs. The cytotoxic transcription factors Runx3 and T-bet mediation enhanced antitumor responses by CD147 CD8 T cells. Moreover, CD147 deletion in T cells increased the frequency of T-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Analysis of tumor tissue samples from patients with non-small-cell lung cancer showed negative correlations between CD147 expression on CD8 TILs and the abundance of CD8 TILs, histological grade of the tumor tissue samples, and survival of patients with advanced tumors. Altogether, we found a novel function of CD147 as a negative regulator of antitumor responses mediated by CD8 TILs and identified CD147 as a potential target for cancer immunotherapy.

Anti-tumor immunity CD147 CD8+ T cells

SCI

英语

通讯

National Natural Science Foundation of China[81572802] ; National Basic Research Program of China[2015CB553700] ; Fourth Military Medical University Foundation for Development of Science and Technology[2019XB005]

Immunology

Immunology

WOS:000588579700003

NATURE PUBLISHING GROUP

2-s2.0-85095836895

Scopus

1.National Translational Science Center for Molecular Medicine & Department of Cell Biology,Fourth Military Medical University,Xi’an,710032,China
2.Medical Research Center,Southern University of Science and Technology Hospital,Shenzhen,518055,China
3.Center of Anesthesiology & Operation,Chinese PLA General Hospital,Beijing,100853,China
4.Department of Radiation Oncology,First Peoples’ Hospital of Changzhou,Third Affiliated Hospital of Soochow University,Changzhou,213000,China
5.Department of Gastroenterology,Henan Children’s Hospital,Zhengzhou,450018,China

Chen，Yatong,Xu，Jing,Wu，Xiaodong,et al. CD147 regulates antitumor CD8+ T-cell responses to facilitate tumor-immune escape[J]. Cellular & Molecular Immunology,2020.

Chen，Yatong.,Xu，Jing.,Wu，Xiaodong.,Yao，Hui.,Yan，Zhou.,...&Chen，Zhi Nan.(2020).CD147 regulates antitumor CD8+ T-cell responses to facilitate tumor-immune escape.Cellular & Molecular Immunology.

Chen，Yatong,et al."CD147 regulates antitumor CD8+ T-cell responses to facilitate tumor-immune escape".Cellular & Molecular Immunology (2020).