{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:00:30Z","timestamp":1793322030247,"version":"4.5.0"},"reference-count":169,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally, driven by chronic liver disease and a complex tumor microenvironment (TME). Recent advances in spatial omics, single-cell analyses, and AI-driven digital pathology have shed light on the intricate heterogeneity of HCC, highlighting key roles for immune suppression, angiogenesis, and fibrosis in tumor progression. This review synthesizes current epidemiological trends, noting a shift from viral hepatitis to metabolic syndrome as a primary etiology in Western populations, and elucidates how TME components\u2014such as tumor-associated macrophages, cancer-associated fibroblasts, vascular endothelial cells, and immunosuppressive cytokines\u2014contribute to resistance against conventional therapies. We detail the evolution of immunotherapeutic strategies from monotherapy to combination regimens, including dual immune checkpoint blockade and the integration of antiangiogenic agents. Emerging circulating and tissue-based biomarkers offer promise for enhanced patient stratification and real-time monitoring of treatment responses. Collectively, these innovations herald a paradigm shift toward TME-directed precision oncology in HCC, emphasizing the need for multi-targeted approaches to synergistically modulate interacting cellular constituents and ultimately improve clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers17111860","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:09:12Z","timestamp":1748840952000},"page":"1860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Bridging Immune Evasion and Vascular Dynamics for Novel Therapeutic Frontiers in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-724X","authenticated-orcid":false,"given":"Sulin","family":"Wu","sequence":"first","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7396-7058","authenticated-orcid":false,"given":"Namrata","family":"Anand","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhoubo","family":"Guo","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Li","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2652-5503","authenticated-orcid":false,"given":"Marcos","family":"Santiago Figueroa","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Jung","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kelly","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W.","family":"Franses","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Internal Medicine, University of Chicago, 900 E. 57th St., KCBD 7114, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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