Cediranib enhances the transcription of MHC-I by upregulating IRF-1
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:221 |
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| Enthalten in: |
Biochemical pharmacology - 221(2024) vom: 31. März, Seite 116036 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Jie [VerfasserIn] |
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| Links: |
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| Themen: |
Cediranib |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bcp.2024.116036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Zheng, Mingming |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Shijia |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Honghai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Qiong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xiaochun |e verfasserin |4 aut | |
| 700 | 1 | |a He, Qiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Bo |e verfasserin |4 aut | |
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