iScience (May 2024)
LC3-dependent extracellular vesicles promote M-MDSC accumulation and immunosuppression in colorectal cancer
- Ye Gu,
- Qiang Liu,
- Qiaoxian He,
- Qiangsheng Wu,
- Lingyun Li,
- Dongchao Xu,
- Liyun Zheng,
- Lu Xie,
- Sile Cheng,
- Hongzhang Shen,
- Yifeng Zhou,
- Jianfeng Yang,
- Hangbin Jin,
- Xiaofeng Zhang
Affiliations
- Ye Gu
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China; Hangzhou Hospital & Institute of Digestive Diseases, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China; Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
- Qiang Liu
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Qiaoxian He
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Qiangsheng Wu
- Department of Assay Development, EOTOBio TECHNOLOGY CO., LTD, Nanjing, Jiangsu 310006, P.R. China
- Lingyun Li
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Dongchao Xu
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Liyun Zheng
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Lu Xie
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Sile Cheng
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Hongzhang Shen
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Yifeng Zhou
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Jianfeng Yang
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Hangbin Jin
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China
- Xiaofeng Zhang
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang, P.R. China; Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China; Hangzhou Hospital & Institute of Digestive Diseases, Hangzhou, Zhejiang 310006, P.R. China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China; Corresponding author
- Journal volume & issue
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Vol. 27,
no. 5
p. 109272
Abstract
Summary: For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC.
