Academic Journal
EGCG Inhibits Tumor Growth in Melanoma by Targeting JAK-STAT Signaling and Its Downstream PD-L1/PD-L2-PD1 Axis in Tumors and Enhancing Cytotoxic T-Cell Responses
| العنوان: | EGCG Inhibits Tumor Growth in Melanoma by Targeting JAK-STAT Signaling and Its Downstream PD-L1/PD-L2-PD1 Axis in Tumors and Enhancing Cytotoxic T-Cell Responses |
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| المؤلفون: | Dinoop Ravindran Menon, Yang Li, Takeshi Yamauchi, Douglas Grant Osborne, Prasanna Kumar Vaddi, Michael F Wempe, Zili Zhai, Mayumi Fujita |
| المصدر: | Pharmaceuticals, Vol 14, Iss 11, p 1081 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
| مصطلحات موضوعية: | EGCG, PD-L1, PD-L2, melanoma immunotherapy, IFN-γ signaling, JAK-STAT signaling, Medicine, Pharmacy and materia medica, RS1-441 |
| الوصف: | Over the last decade, therapies targeting immune checkpoints, such as programmed death-1 (PD-1), have revolutionized the field of cancer immunotherapy. However, low response rates and immune-related adverse events remain a major concern. Here, we report that epigallocatechin gallate (EGCG), the most abundant catechin in green tea, inhibits melanoma growth by modulating an immune response against tumors. In vitro experiments revealed that EGCG treatment inhibited interferon-gamma (IFN-γ)-induced PD-L1 and PD-L2 expression and JAK-STAT signaling. We confirmed that this effect was driven by inhibiting STAT1 gene expression and STAT1 phosphorylation, thereby downregulating the PD-L1/PD-L2 transcriptional regulator IRF1 in both human and mouse melanoma cells. Animal studies revealed that the in vivo tumor-inhibitory effect of EGCG was through CD8+ T cells and that the inhibitory effect of EGCG was comparable to anti-PD-1 therapy. However, their mechanisms of action were different. Dissimilar to anti-PD-1 treatment that blocks PD-1/PD-L1 interaction, EGCG inhibited JAK/STAT signaling and PD-L1 expression in tumor cells, leading to the re-activation of T cells. In summary, we demonstrate that EGCG enhances anti-tumor immune responses by inhibiting JAK-STAT signaling in melanoma. EGCG could be used as an alternative treatment strategy to target the PD-L1/PD-L2-PD-1 axis in cancers. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-8247 |
| Relation: | https://www.mdpi.com/1424-8247/14/11/1081; https://doaj.org/toc/1424-8247 |
| DOI: | 10.3390/ph14111081 |
| URL الوصول: | https://doaj.org/article/6cf323d74bc0482fa07dc2a10f04c798 |
| رقم الانضمام: | edsdoj.6cf323d74bc0482fa07dc2a10f04c798 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14248247 |
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| DOI: | 10.3390/ph14111081 |