期刊
ORGANIC GEOCHEMISTRY
卷 175, 期 -, 页码 112-121出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bbrc.2023.01.005
关键词
Regulatory B cells; Exosome; HOTAIR; PDL1; CRC
Tumor-derived exosomes drive Bregs to suppress anti-tumor immunity by delivering lncRNA HOTAIR, which activates the STAT3 pathway and induces PDL1 expression in B cells. The presence of exosomal HOTAIR is positively correlated with tumor-infiltrating PDL1+ B cells in CRC patients.
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.(c) 2023 Elsevier Inc. All rights reserved.
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