1. Crosstalk between regulated cell death and immunity in redox dyshomeostasis for pancreatic cancer.
- Author
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Zhou, Zhaokai, Zhang, Yuyuan, Li, Jing, Weng, Siyuan, Li, Jie, Chen, Shuang, Lv, Jinxiang, Xu, Nuo, Zhang, Yanping, Yang, Shuai, Wang, Zhan, Han, Xinwei, Liu, Zaoqu, and Wen, Jianguo
- Subjects
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PANCREATIC cancer , *HOMEOSTASIS , *APOPTOSIS , *PROGRAMMED cell death 1 receptors , *CELL death , *OXIDATION-reduction reaction , *IMMUNITY , *THERAPEUTICS - Abstract
The insidious clinical symptoms of pancreatic cancer (PACA), extensive tolerance to radiotherapy and chemotherapy, and insensitivity to immunotherapy result in an inferior prognosis. Redox dyshomeostasis could trigger programmed cell death and contribute to functional changes in immune cells, which is strongly associated with tumorigenesis and tumor development. Therefore, it is warranted to decipher the crosstalk between regulated cell death and immunity in the context of redox dyshomeostasis for PACA. Herein, four redox-related subtypes of PACA were identified: C1 and C2 displayed malignant phenotypes with dismal clinical outcomes, conspicuous enrichment in cell death pathways, high redox score, low immune activation, and "immune-desert" tumor immune microenvironment (TIME); C3, an immune-rejection/excluded subtype, with abundant immune cells, high co-stimulatory, co-inhibitory, and MHC molecules, and potential response to immunotherapy; C4, with the best prognosis, low redox pattern, high level of autophagy, low enrichment of most cell death-related pathways, and "immune-hot" TIME. Overall, this study found an attractive platform from the perspective of redox-related pathways, which would propose insights into the intricate and elaborate molecular mechanisms of PACA and offer more effective and tailored intervention protocols. • The higher basal oxidative state in PACA was related to higher programmed cell death signals, conducting an "immune-cold" TIME. • Relatively low levels of redox state portended favorable clinical outcomes in PACA patients. • ROS manipulation treatment may be a novel potential therapeutic approach for C1 and C2 patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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