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
  • 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.
Products
Inhibitors & Agonists
Other Products