Crosstalk between regulated cell death and immunity in redox dyshomeostasis for pancreatic cancer

Zhaokai Zhou; Yuyuan Zhang; Jing Li; Siyuan Weng; Jie Li; Shuang Chen; Jinxiang Lv; Nuo Xu; Yanping Zhang; Shuai Yang; Zhan Wang; Xinwei Han; Zaoqu Liu; Jianguo Wen

doi:10.1016/j.cellsig.2023.110774

Crosstalk between regulated cell death and immunity in redox dyshomeostasis for pancreatic cancer

Cell Signal. 2023 Sep:109:110774. doi: 10.1016/j.cellsig.2023.110774. Epub 2023 Jun 17.

Authors

Zhaokai Zhou¹, Yuyuan Zhang², Jing Li², Siyuan Weng², Jie Li², Shuang Chen³, Jinxiang Lv⁴, Nuo Xu⁵, Yanping Zhang¹, Shuai Yang¹, Zhan Wang¹, Xinwei Han⁶, Zaoqu Liu⁷, Jianguo Wen⁸

Affiliations

¹ Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Henan 450052, China.
² Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Interventional Institute of Zhengzhou University, Zhengzhou, Henan 450052, China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan 450052, China.
³ Center of Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁴ Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁵ Reproductive Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁶ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Interventional Institute of Zhengzhou University, Zhengzhou, Henan 450052, China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan 450052, China. Electronic address: fcchanxw@zzu.edu.cn.
⁷ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Interventional Institute of Zhengzhou University, Zhengzhou, Henan 450052, China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan 450052, China. Electronic address: liuzaoqu@163.com.
⁸ Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Henan 450052, China. Electronic address: wenjg@hotmail.com.

PMID: 37331416
DOI: 10.1016/j.cellsig.2023.110774

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.

Keywords: Immune microenvironment; Immunotherapy; Molecular subtypes; Pancreatic cancer; Redox dyshomeostasis; Regulated cell death.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Death
Humans
Oxidation-Reduction
Pancreatic Neoplasms*
Regulated Cell Death*
Tumor Microenvironment