{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:40:07Z","timestamp":1790822407674,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82204814"],"award-info":[{"award-number":["82204814"]}]},{"name":"National Natural Science Foundation of China","award":["2025A1515012841"],"award-info":[{"award-number":["2025A1515012841"]}]},{"name":"National Natural Science Foundation of China","award":["2025A1515012216"],"award-info":[{"award-number":["2025A1515012216"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["82204814"],"award-info":[{"award-number":["82204814"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2025A1515012841"],"award-info":[{"award-number":["2025A1515012841"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2025A1515012216"],"award-info":[{"award-number":["2025A1515012216"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Major histocompatibility complex class I (MHC-I)-mediated antigen presentation plays a pivotal role in anti-tumor immunity by enabling CD8+ T cells to recognize and eliminate malignant cells. In melanoma, modulation of this pathway is critical for improving the efficacy of immunotherapies. Our study demonstrates that the natural compound Cepharanthine (CEP) exhibits notable antitumor activity by enhancing MHC-I-mediated antigen presentation. CEP treatment upregulated MHC-I expression (both membrane-bound and total levels) in melanoma cells in a concentration-dependent manner, thereby improving antigen-presenting capacity. Interestingly, when autophagy was pharmacologically blocked using Bafilomycin A1, co-treatment with CEP did not lead to further elevation of MHC-I expression, suggesting that CEP\u2019s effect is mediated through disruption of the autophagic pathway. Mechanistically, CEP induced autophagosome accumulation, as evidenced by an increase in GFP-LC3 puncta. Fluorescence imaging further confirmed that CEP selectively impaired lysosomal acidification without affecting autophagosome\u2013lysosome fusion, thereby inhibiting late-stage autophagic flux. Furthermore, CEP treatment promoted CD8+ T cell infiltration into tumor tissues and enhanced the antitumor efficacy of anti-PD-1 therapy, resulting in greater tumor suppression compared to either treatment alone. The study elucidates how CEP\u2019s selective lysosomal inhibition creates a tumor microenvironment more susceptible to immune surveillance, primarily through preserved MHC-I surface expression and subsequent T cell recognition. This work highlights CEP as a promising immunomodulatory agent and provides a potential strategy for improving the outcomes of immune checkpoint blockade therapy.<\/jats:p>","DOI":"10.3390\/cells14161231","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T08:10:32Z","timestamp":1754899832000},"page":"1231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cepharanthine Enhances MHC-I Antigen Presentation and Anti-Tumor Immunity in Melanoma via Autophagy Inhibition"],"prefix":"10.3390","volume":"14","author":[{"given":"He","family":"Luo","sequence":"first","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingye","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Du","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixian","family":"Lv","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 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