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However, suboptimal overall response rates persist alongside dual challenges: immune\u2010related toxicities and immunosuppressive tumor microenvironment. Combination therapies represent a pivotal strategy to overcome these limitations. In recent years, traditional Chinese medicine has gained significant attention. Elemene, a small\u2010molecule compound derived from\n                    <jats:italic>Curcuma wenyujin<\/jats:italic>\n                    , has garnered attention for its immunomodulatory potential and demonstrates clinical efficacy in combination therapies. Nevertheless, its synergistic mechanisms with immunotherapy remain incompletely characterized. This study demonstrates for the first time that elemene modulates the miR\u2010130a\u20105p\/SPP\/MHC\u2010I axis, resulting in an enhanced diversity and abundance of antigen\/MHC\u2010I complexes on the surface of HCC cells. This mechanism promotes the recognition and elimination of HCC cells by cytotoxic T lymphocytes, thereby augmenting the antitumor immune efficacy of PD\u20101. Moreover, the functional significance of the miR\u2010130a\u20105p\/SPP\/MHC\u2010I axis in modulating the tumor immune microenvironment is systematically validated through in vitro and in vivo HCC models, as well as in clinical patient specimens. These findings underscore the potential of combining elemene with anti\u2010PD\u20101 therapy as a safe and effective treatment strategy for HCC, offering significant translational promise for improving patient outcomes.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511887","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T12:00:05Z","timestamp":1768219205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Elemene Augments the Effects of Anti\u2010PD\u20101 Immunotherapy on Hepatocellular Carcinoma by Regulating the miR\u2010130a\u20105p\/SPP\/MHC\u2010I Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Menglan","family":"Wang","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Anti\u2010Cancer Chinese Medicines and Natural Medicines School of Pharmacy Hangzhou Normal University Department of Hepatology the Affiliated Hospital of 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