{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:25:21Z","timestamp":1790673921102,"version":"4.1.0"},"reference-count":134,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Startup Research Fund of Henan Academy of Sciences","award":["241828237"],"award-info":[{"award-number":["241828237"]}]},{"award":["241828237"],"award-info":[{"award-number":["241828237"]}],"id":[{"id":"https:\/\/ror.org\/00hy87220","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation Youth Fund Project of Henan","award":["252300420686"],"award-info":[{"award-number":["252300420686"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) arises predominantly in chronic liver disease with a uniquely tolerogenic microenvironment. Immune checkpoint inhibitors (ICIs) have improved the prognosis of advanced HCC, yet most patients exhibit low response rates or therapeutic resistance due to the highly immunosuppressive tumor microenvironment. Metabolic reprogramming is not only a core hallmark of HCC but also a key regulatory axis connecting tumor cells and the immune system. HCC cells exhibit pronounced Warburg glycolysis, upregulated glutaminolysis, aberrant lipid storage and oxidation, enhanced ketone metabolism, and altered polyamine flux. These metabolic alterations lead to nutrient competition, lactate accumulation, amino acid depletion, and oncometabolite signaling, resulting in T cell exhaustion, macrophage polarization, T cell expansion, and impaired dendritic cell function, thereby influencing tumor progression, immune escape, and therapeutic resistance. Targeting metabolic\u2013immune crosstalk represents a promising strategy for reversing immunosuppression and enhancing the efficacy of immunotherapy. In this review, we systematically summarize the core patterns of metabolic reprogramming in HCC, dissect the molecular mechanisms of metabolic crosstalk at the tumor\u2013immune interface, and discuss the role of immunometabolic remodeling in therapeutic resistance. This review aims to provide a comprehensive theoretical basis and new research directions for improving the efficacy of HCC treatment by targeting the metabolic\u2013immune regulatory axis.<\/jats:p>","DOI":"10.3390\/cells15151357","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:45:26Z","timestamp":1785239126000},"page":"1357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Reprogramming at the Tumor\u2013Immune Interface in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Weiming","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Henan Academy of Sciences, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Henan Academy of Sciences, Zhengzhou 450046, China"},{"name":"College of Life Science, Henan Normal University, Xinxiang 453007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","first-page":"14","article-title":"Hepatocellular carcinoma: Epidemiology, diagnosis and treatment","volume":"7","author":"Mauro","year":"2010","journal-title":"JHEP Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1152\/physrev.00004.2023","article-title":"The liver as a central \u201chub\u201d of the immune system: Pathophysiological implications","volume":"105","author":"Ronca","year":"2025","journal-title":"Physiol. 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