2. Academic Validation
  3. Exosomal lncRNA HOTAIR induces PDL1+ B cells to impede anti-tumor immunity in colorectal cancer

Exosomal lncRNA HOTAIR induces PDL1+ B cells to impede anti-tumor immunity in colorectal cancer

  • Biochem Biophys Res Commun. 2023 Feb 12:644:112-121. doi: 10.1016/j.bbrc.2023.01.005.
Zhangjuan Xie 1,  Jie Xia 1,  Mengxia Jiao 1,  Pengyuan Zhao 1,  Zhiqiang Wang 2,  Shengli Lin 3,  Yun Xing 1,  Yifan Li 4,  Zhou Lu 5,  Ziwen Zhong 5,  Changhong Miao 5,  Pinghong Zhou 3,  Jiawen Qian 6,  Luman Wang 4,  Dan Zhang 1,  Jie Gu 3,  Yiwei Chu 7,  Ronghua Liu 8
Affiliations

Affiliations

  • 1 Shanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
  • 2 Shanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Department of Immunology, School of Basic Medical Sciences and Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
  • 3 Endoscopy Center and Endoscopy Research Institute and Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 4 Department of Immunology, School of Basic Medical Sciences and Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
  • 5 Liver Cancer Institute and Department of Anesthesiology, Department of Endocrinology, Zhongshan Hospital, Shanghai, 200032, China.
  • 6 Department of Immunology, School of Basic Medical Sciences and Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Biotherapy Research Center, Fudan University, Shanghai, 200032, China.
  • 7 Department of Immunology, School of Basic Medical Sciences and Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Liver Cancer Institute and Department of Anesthesiology, Department of Endocrinology, Zhongshan Hospital, Shanghai, 200032, China. Electronic address: [email protected].
  • 8 Shanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. Electronic address: [email protected].
PMID: 36640665 DOI: 10.1016/j.bbrc.2023.01.005
Abstract

Regulatory B cells (Bregs) contribute to tumor immunosuppression. However, how B cells acquire their regulatory features in tumors remain unclear. Exosomes are important messengers that transmit tumor information to remodel tumor immunity. Here we revealed that tumor-derived exosomes drive Bregs to suppress anti-tumor immunity by delivering long non-coding RNAs (lncRNAs). HOTAIR was screened by lncRNA profiling in both colorectal Cancer (CRC)-derived exosomes and infiltrating B cells. Tumor-derived HOTAIR polarized B cells toward a regulatory feature marked by programmed cell death-ligand 1 (PDL1) in CRC, and induced PDL1+ B cells to suppress CD8+ T cell activity. Exosomal HOTAIR bound to and protected Pyruvate Kinase M2 (PKM2) against ubiquitination degradation, resulting in STAT3 activation and PDL1 expression. Results from CRC patients showed a positive correlation between exosomal HOTAIR and tumor-infiltrating PDL1+ B cells. These findings reveal how B cells acquire PDL1-dominant regulatory feature in CRC, implying the clinical significance of exosomal therapy targeting HOTAIR.

Keywords

CRC; Exosome; HOTAIR; PDL1; Regulatory B cells.

Figures
Products
Inhibitors & Agonists
Other Products