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Cediranib enhances the transcription of MHC-I by upregulating IRF-1.
- Source :
-
Biochemical Pharmacology . Mar2024, Vol. 221, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- [Display omitted] Diminished or lost Major Histocompatibility Complex class I (MHC-I) expression is frequently observed in tumors, which obstructs the immune recognition of tumor cells by cytotoxic T cells. Restoring MHC-I expression by promoting its transcription and improving protein stability have been promising strategies for reestablishing anti-tumor immune responses. Here, through cell-based screening models, we found that cediranib significantly upregulated MHC-I expression in tumor cells. This finding was confirmed in various non-small cell lung cancer (NSCLC) cell lines and primary patient-derived lung cancer cells. Furthermore, we discovered cediranib achieved MHC-I upregulation through transcriptional regulation. interferon regulatory factor 1 (IRF-1) was required for cediranib induced MHC-I transcription and the absence of IRF-1 eliminated this effect. Continuing our research, we found cediranib triggered STAT1 phosphorylation and promoted IRF-1 transcription subsequently, thus enhancing downstream MHC-I transcription. In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8+ T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00062952
- Volume :
- 221
- Database :
- Academic Search Index
- Journal :
- Biochemical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 175724590
- Full Text :
- https://doi.org/10.1016/j.bcp.2024.116036