Inverse correlation between TP53 gene status and PD-L1 protein levels in a melanoma cell model depends on an IRF1/SOX10 regulatory axis
We show that p53 loss influences the level of PD-L1 through IRF1 and SOX10 in an isogenic melanoma cell model, and that p53 loss affects NK-cell cytotoxicity toward tumor cells. Moreover, activation of p53 by MDM2 inhibition has a complex effect on IRF1/PD-L1 activation. These findings indicate that evaluation of p53 status in patients with melanoma will be important for predicting the response to PD-L1 monotherapy and/or dual treatments where p53 pathways participate in the overall response.
Authors
- Zuzana Tylichová (ORCID: https://orcid.org/0000-0003-0433-5505)
- Filip Zavadil-Kokas
- Philip J. Coates (ORCID: https://orcid.org/0000-0003-1518-6306)
- Bořivoj Vojtěšek (ORCID: https://orcid.org/0000-0001-6194-3705)
- Martina Kucerikova
- Nela Friedlová (ORCID: https://orcid.org/0009-0006-5593-7222)
- Pavlína Zatloukalová
- Ted R. Hupp (ORCID: https://orcid.org/0000-0003-0391-0352)
- Lucia Martinkova
Institutions
- Masaryk University (CZ)
- Edinburgh Cancer Research (GB)
- Masaryk Memorial Cancer Institute (CZ)
- Institute of Genetics and Cancer (GB)
Publication Details
- Journal
- Cellular & Molecular Biology Letters
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1186/s11658-024-00637-y
- Citations
- 12
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 3.39
Funders
- European Commission
- Grantová Agentura České Republiky
- Ministerstvo Zdravotnictví Ceské Republiky