Regulation of CD8+ T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer

Autor: Jiayin Sun, Hui Zhang, Wenjie Wei, Xingyuan Xiao, Chao Huang, Liang Wang, He Zhong, Yangkai Jiang, Fuxin Zheng, Hongmei Yang, Guosong Jiang, Xiaoping Zhang
Rok vydání: 2023
Předmět:
Zdroj: Oncogene. 42:1247-1262
ISSN: 1476-5594
0950-9232
Popis: The limited success of immunotherapies targeting immune checkpoint inhibitors is largely ascribed to the lack of infiltrating CD8+ T lymphocytes. Circular RNAs (circRNAs) are a novel type of prevalent noncoding RNA that have been implicated in tumorigenesis and progression, while their roles in modulating CD8+ T cells infiltration and immunotherapy in bladder cancer have not yet been investigated. Herein, we uncover circMGA as a tumor-suppressing circRNA triggering CD8+ T cells chemoattraction and boosting the immunotherapy efficacy. Mechanistically, circMGA functions to stabilize CCL5 mRNA by interacting with HNRNPL. In turn, HNRNPL increases the stability of circMGA, forming a feedback loop that enhances the function of circMGA/HNRNPL complex. Intriguingly, therapeutic synergy between circMGA and anti-PD-1 could significantly suppress xenograft bladder cancer growth. Taken together, the results demonstrate that circMGA/HNRNPL complex may be targetable for cancer immunotherapy and the study advances our understanding of the physiological roles of circRNAs in antitumor immunity.
Databáze: OpenAIRE
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