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Regulation of CD8+T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer
- Source :
- Oncogene; April 2023, Vol. 42 Issue: 15 p1247-1262, 16p
- Publication Year :
- 2023
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Volume :
- 42
- Issue :
- 15
- Database :
- Supplemental Index
- Journal :
- Oncogene
- Publication Type :
- Periodical
- Accession number :
- ejs62422180
- Full Text :
- https://doi.org/10.1038/s41388-023-02637-2