Frontiers in Immunology (Sep 2022)
A new personalized vaccine strategy based on inducing the pyroptosis of tumor cells in vivo by transgenic expression of a truncated GSDMD N-terminus
- Jinrong He,
- Peng Zheng,
- Yongjun Chen,
- Jialong Qi,
- Jialong Qi,
- Chao Ye,
- Duo Li,
- Duo Li,
- Ying Yang,
- Ying Yang,
- Ying Yang,
- Qingwen Liu,
- Qingwen Liu,
- Yongmao Hu,
- Yongmao Hu,
- Xiao Zheng,
- Xiao Zheng,
- Weiran Li,
- Liangqun Hua,
- Liangqun Hua,
- Zhongqian Yang,
- Haoqian Chen,
- Haoqian Chen,
- Weiwei Huang,
- Wenjia Sun,
- Xu Yang,
- Qiong Long,
- Hongmei Bai,
- Yanbing Ma
Affiliations
- Jinrong He
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Peng Zheng
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Yongjun Chen
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Jialong Qi
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Jialong Qi
- Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Kunming, China
- Chao Ye
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Duo Li
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Duo Li
- Department of Acute Infectious Diseases Control and Prevention, Yunnan Provincial Center for Disease Control and Prevention, Kunming, China
- Ying Yang
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Ying Yang
- Institute of Medical Biology, Kunming Medical University, Kunming, China
- Ying Yang
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Qingwen Liu
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Qingwen Liu
- Institute of Medical Biology, Kunming Medical University, Kunming, China
- Yongmao Hu
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Yongmao Hu
- School of Life Sciences, Yunnan University, Kunming, China
- Xiao Zheng
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Xiao Zheng
- School of Life Sciences, Yunnan University, Kunming, China
- Weiran Li
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Liangqun Hua
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Liangqun Hua
- School of Life Sciences, Yunnan University, Kunming, China
- Zhongqian Yang
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Haoqian Chen
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Haoqian Chen
- School of Ethnic Medicine, Yunnan Minzu University, Kunming, China
- Weiwei Huang
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Wenjia Sun
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Xu Yang
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Qiong Long
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Hongmei Bai
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Yanbing Ma
- Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- DOI
- https://doi.org/10.3389/fimmu.2022.991857
- Journal volume & issue
-
Vol. 13
Abstract
The variability and heterogeneity of tumor antigens and the tumor-driven development of immunosuppressive mechanisms leading to tumor escape from established immunological surveillance. Here, the tumor cells were genetically modified to achieve an inducible overexpression of the N-terminal domain of gasdermin D (GSDMD-NT) and effectively cause pyroptosis under a strict control. Pyroptotic tumor cells release damage-associated molecular patterns (DAMPs) and inflammatory cytokines to promote the maturation and migration of bone marrow-derived dendritic cells (BMDCs). Furthermore, local tumor delivery, and preventive or therapeutic subcutaneous immunization of the modified cells, followed by the induction of GSDMD-NT expression, significantly stimulated both the systemic and local responses of antitumor immunity, and reprogrammed the tumor microenvironment, leading to the dramatic suppression of tumor growth in mice. This study has explored the application potency of inducing the pyroptosis of tumor cells in the field of tumor immunotherapy, especially for developing a new and promising personalized tumor vaccine.
Keywords
