{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:41:22Z","timestamp":1790606482441,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81930102 81773754"],"award-info":[{"award-number":["81930102 81773754"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Programmed death ligand 1 (PD-L1) which is upregulated in various epithelial tumors, plays a central role in the evasion of the immune system. In addition to monoclonal antibodies that blocking PD1\/PD-L1 axis, finding small molecule compounds that can suppress PD-L1 expression might be another substitutable strategy for PD1\/PD-L1 based therapy. Here, we found that dihydropyridine calcium channel blockers dose-dependently reduced the expression of PD-L1, both in the cytoplasm and cell surface. IFN\u03b3 induced PD-L1 transcription was consistently suppressed by Lercanidipine in 24\u00a0h, whereas, the half-life of PD-L1 protein was not significantly affected. IFN\u03b3 trigged significant STAT1 phosphorylation, which was eliminated by Lercanidipine. Similarly, STAT1 phosphorylation could also be abolished by extracellular calcium chelating agent EGTA and intracellular calcium chelator BAPTA-AM. Furthermore, Lercanidipine enhanced killing ability of T cells by down-regulating PD-L1. Taken together, our studies suggest that calcium signal is a crucial factor that mediates the transcription of PD-L1 and regulation of calcium can be used as a potential strategy for PD-L1 inhibition.<\/jats:p>","DOI":"10.3389\/fphar.2020.539261","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T05:16:11Z","timestamp":1610601371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Dihydropyridine Calcium Channel Blockers Suppress the Transcription of PD-L1 by Inhibiting the Activation of STAT1"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaohui","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1038\/leu.2017.103","article-title":"PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma","volume":"31","author":"Atsaves","year":"2017","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15894","DOI":"10.18632\/oncotarget.15213","article-title":"PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p","volume":"8","author":"Audrito","year":"2017","journal-title":"Oncotarget"},{"key":"B3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s11912-017-0627-0","article-title":"Immunotherapy in breast cancer: the emerging role of PD-1 and PD-L1","volume":"19","author":"Bertucci","year":"2017","journal-title":"Curr. 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