title: Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients.
abstract: T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8+T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8+T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells. Furthermore, TIM-3+CEACAM1+CD8+T cells represented the most dysfunctional population with the least IFN-γ production. In addition, the expressions of TIM-3 and CEACAM1 were correlated with advanced stage and could be independent risk factors for CRC. We for the first time to our knowledge suggested that co-expression of TIM-3 and CEACAM1 can mediate T cell exhaustion and may be potential biomarkers for CRC prediction, highlighting the possibility of being immunotherapy targets.
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Cai
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Central Medical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Chang
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: katelinwang@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: lihuahu@hust.edu.cn.
authors.forename: Lihua
authors.initials: L
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007371:Interferon-gamma
keywords: CEACAM1; Colorectal cancer; Immunosuppression; T cell exhaustion; TIM-3