A chemical screen underscores the essential role of STAT1-dependent IFNγ signaling to regulate HLA-I expression in cancer cells.
| Autor: | Barz M; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Porebski B; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Panshikar P; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Häggbladd M; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Hühn D; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Fernandez-Capetillo O; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.; Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. |
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| Jazyk: | angličtina |
| Zdroj: | MicroPublication biology [MicroPubl Biol] 2023 Jan 18; Vol. 2023. Date of Electronic Publication: 2023 Jan 18 (Print Publication: 2023). |
| DOI: | 10.17912/micropub.biology.000697 |
| Abstrakt: | The presentation of neoantigens by HLA-I is essential for the recognition of tumor cells by cytotoxic T cells. Transcriptionally, HLA-I expression is regulated by interferon-dependent activation of JAK/STAT signaling. Accordingly, mutations that inactivate this pathway are one of the main causes of resistance to cancer immunotherapies. Recent evidences indicate that HLA-I expression can be induced independently of IFN-signaling by the innate immune response. In this context, we performed an image-based screen to evaluate how more than 5,000 chemicals, including all medically available drugs plus many others in advanced preclinical development, influence HLA-I expression in STAT1-deficient cells. Our screening failed to identify any significant hits, suggesting that drug-dependent modulation of HLA-I expression is strictly dependent on IFN-signaling. (Copyright: © 2023 by the authors.) |
| Databáze: | MEDLINE |
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