Pyroptosis: a new paradigm of cell death for fighting against cancer

Journal of Experimental & Clinical Cancer Research

Jianbo Yang¹  Xiayu Li²  Mei Yi³  Zhaoyang Zeng⁴  Wei Xiong⁴  Xiaoling Li⁴  Guiyuan Li⁴  Quanzhu Chen⁴  Bo Xiang⁴  Yixin Tan⁵ 

[1] Department of Laboratory Medicine and Pathology, University of Minnesota, 55455, Minneapolis, MN, USA;Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China;NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, 410013, Changsha, Hunan, China;The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, 410078, Changsha, Hunan, China;Department of Dermatology, Xiangya Hospital, The Central South University, 410008, Changsha, Hunan, China;NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, 410013, Changsha, Hunan, China;The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, 410078, Changsha, Hunan, China;Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China;NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, 410013, Changsha, Hunan, China;The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, 410078, Changsha, Hunan, China;Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China;Department of Dermatology, The Second Xiangya Hospital, The Central South University, 410011, Changsha, Hunan, China;

关键词: Tumor microenvironment;    Gasdermin;    Necroptosis;    Ferroptosis;    Immune checkpoint;    Adaptive immunity;    Immunogenic cell death;   

DOI  :  10.1186/s13046-021-01959-x

来源: Springer

【 摘 要 】

BackgroundUnraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.Main bodyPyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.ConclusionIn this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.

【 授权许可】

CC BY