دورية أكاديمية
Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1 ; Cancers
| العنوان: | Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1 ; Cancers |
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| المؤلفون: | Khazan, Negar, Quarato, Emily, Singh, Niloy, Snyder, Cameron, Moore, Taylor, Miller, John, Yasui, Masato, Teramoto, Yuki, Goto, Takuro, Reshi, Sabeeha, Hong, Jennifer, Zhang, Naixin, Pandey, Diya, Srivastava, Priyanka, Morell, Alexandra, Kawano, Hiroki, Kawano, Yuko, Conley, Thomas, Sahasrabudhe, Deepak, Yano, Naohiro, Miyamoto, Hiroshi, Aljitawi, Omar, Liesveld, Jane, Becker, Michael, Calvi, Laura, Zhovmer, Alexander, Tabdanov, Erdem, Dokholyan, Nikolay, Linehan, David, Hansen, Jeanne, Gerber, Scott, Sharon, Ashoke, Khera, Manoj, Jurutka, Peter, Rochel, Natacha, Kim, Kyu Kwang, Rowswell-Turner, Rachael, Singh, Rakesh, Moore, Richard |
| المساهمون: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 2072-6694. |
| بيانات النشر: | HAL CCSD MDPI |
| سنة النشر: | 2023 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | PD-L1 AML MDS vitamin D VDR small molecule M2H assay efferocytosis, PD-L1, AML, MDS, vitamin D, VDR, small molecule, M2H assay, efferocytosis, [SDV]Life Sciences [q-bio] |
| الوصف: | Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-04274207; https://hal.science/hal-04274207Test; https://hal.science/hal-04274207/documentTest; https://hal.science/hal-04274207/file/cancers2023.pdfTest |
| DOI: | 10.3390/cancers15133432 |
| الإتاحة: | https://doi.org/10.3390/cancers15133432Test https://hal.science/hal-04274207Test https://hal.science/hal-04274207/documentTest https://hal.science/hal-04274207/file/cancers2023.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.135C6CDD |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers15133432 |
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