Interleukin-37 promotes colitis-associated carcinogenesis via SIGIRR-mediated cytotoxic T cells dysfunction
作者机构：State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengduSichuan 610041China Department of Liver Surgery&Liver TransplantationWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduSichuan 610041China Laboratory of Liver SurgeryWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Obstetrics and GynecologyWest China Second University HospitalSichuan UniversityChengdu 610041China Key Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationSichuan UniversityChengdu 610041China Department of Cardiovascular MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China Laboratory of Human Disease and ImmunotherapiesWest China HospitalSichuan UniversityChengduSichuan 610041China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2022年第7卷第2期
页 面：502-518页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported by the National Natural Science Foundation of China(81472650,81602763,81573050,82003358,81673061,81703132,31872739,31271483) the Key Research and Development Program of Sichuan Province[2020YFS0271] Project funded by China Postdoctoral Science Foundation(2016M592673,2018M631087,and 2017T100700) the Sichuan Provincial Outstanding Youth Fund(2015JQ0025) the Postdoctoral Fund for West China Hospital(2019HXBH075) the Fundamental Research Funds for the Central Universities(2019SCU12041,the Postdoctoral Foundation of Sichuan University) the National Science and Technology Major Project(2018ZX09733001-001-006 and 2019ZX09201003-003) the Sichuan Science and Technology Program(2021YJ0420)
主 题：immunity cytotoxic Interleukin
摘 要：Interleukin-37b(hereafter called IL-37)was identified as fundamental inhibitor of natural and acquired *** molecular mechanism and function of IL-37 in colorectal cancer(CRC)has been ***,we found that IL-37 transgenic(IL-37tg)mice were highly susceptible to colitis-associated colorectal cancer(CAC)and suffered from dramatically increased tumor burdens in ***,IL-37 is dispensable for intestinal mutagenesis,and CRC cell proliferation,apoptosis,and ***,IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA ***8^(+)T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice,enabling tumor evasion of immune *** dysfunction led by IL-37 antagonizes IL-18–induced proliferation and effector function of CD8+T cells,which was dependent on SIGIRR(single immunoglobulin interleukin-1 receptor-related protein).Finally,we observed that IL-37 levels were significantly increased in CRC patients,and positively correlated with serum CRC biomarker CEA levels,but negatively correlated with the CD8+T cell infiltration in CRC *** findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancerimmunity cycle as therapeutic targets in CRC.
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