دورية أكاديمية
PPARγ induces PD-L1 expression in MSS+ colorectal cancer cells
| العنوان: | PPARγ induces PD-L1 expression in MSS+ colorectal cancer cells |
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| المؤلفون: | Tobias Gutting, Veronika Hauber, Jens Pahl, Kay Klapproth, Wenyue Wu, Ioana Dobrota, Frank Herweck, Juliane Reichling, Laura Helm, Torsten Schroeder, Beifang Li, Philip Weidner, Tianzuo Zhan, Maximilian Eckardt, Johannes Betge, Sebastian Belle, Carsten Sticht, Timo Gaiser, Michael Boutros, Matthias P.A. Ebert, Adelheid Cerwenka, Elke Burgermeister |
| المصدر: | OncoImmunology, Vol 10, Iss 1 (2021) |
| بيانات النشر: | Taylor & Francis Group, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | immunotherapy, cancer, colorectal, pd-l1, ppar, mss, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Only a small subset of colorectal cancer (CRC) patients benefits from immunotherapies, comprising blocking antibodies (Abs) against checkpoint receptor “programmed-cell-death-1” (PD1) and its ligand (PD-L1), because most cases lack the required mutational burden and neo-antigen load caused by microsatellite instability (MSI) and/or an inflamed, immune cell-infiltrated PD-L1+ tumor microenvironment. Peroxisome proliferator-activated-receptor-gamma (PPARγ), a metabolic transcription factor stimulated by anti-diabetic drugs, has been previously implicated in pre/clinical responses to immunotherapy. We therefore raised the hypothesis that PPARγ induces PD-L1 on microsatellite stable (MSS) tumor cells to enhance Ab-target engagement and responsiveness to PD-L1 blockage. We found that PPARγ-agonists upregulate PD-L1 mRNA/protein expression in human gastrointestinal cancer cell lines and MSS+ patient-derived tumor organoids (PDOs). Mechanistically, PPARγ bound to and activated DNA-motifs similar to cognate PPARγ-responsive-elements (PPREs) in the proximal −2 kb promoter of the human PD-L1 gene. PPARγ-agonist reduced proliferation and viability of tumor cells in co-cultures with PD-L1 blocking Ab and lymphokine-activated killer cells (LAK) derived from the peripheral blood of CRC patients or healthy donors. Thus, metabolic modifiers improved the antitumoral response of immune checkpoint Ab, proposing novel therapeutic strategies for CRC. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162-402X 2162402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2021.1906500 |
| URL الوصول: | https://doaj.org/article/76d82438b7e2457c9fd5fa68a566c022 |
| رقم الأكسشن: | edsdoj.76d82438b7e2457c9fd5fa68a566c022 |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2021.1906500 |