热空气
癌症研究
微泡
结直肠癌
生物
调节性B细胞
肿瘤微环境
外体
免疫系统
小RNA
长非编码RNA
癌症
免疫学
下调和上调
白细胞介素10
肿瘤细胞
基因
生物化学
遗传学
作者
Zhangjuan Xie,Jie Xia,Mengxia Jiao,Pengyuan Zhao,Zhiqiang Wang,Shengli Lin,Yun Xing,Yifan Li,Lu Zhou,Ziwen Zhong,Changhong Miao,Ping‐Hong Zhou,Jiawen Qian,Luman Wang,Dan Zhang,Jie Gu,Yiwei Chu,Ronghua Liu
标识
DOI:10.1016/j.bbrc.2023.01.005
摘要
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.
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