{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:19:58Z","timestamp":1790295598612,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["T325R32DK007639-28; 1RO1DK125730-01A1"],"award-info":[{"award-number":["T325R32DK007639-28; 1RO1DK125730-01A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"The University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["P50 CA217674"],"award-info":[{"award-number":["P50 CA217674"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008013","name":"The University of Texas Medical Branch at Galveston","doi-asserted-by":"publisher","award":["2014-07 and LIME 19016"],"award-info":[{"award-number":["2014-07 and LIME 19016"]}],"id":[{"id":"10.13039\/100008013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The role of tumor-associated macrophages (TAMs) in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. Most studies rely on platforms that remove intrahepatic macrophages from the microenvironment prior to evaluation. Cell isolation causes activation and phenotypic changes that may not represent their actual biology and function in situ. State-of-the-art methods provides new strategies to study TAMs without losing the context of tissue architecture and spatial relationship with neighboring cells. These technologies, such as multispectral imaging (e.g., Vectra Polaris), mass cytometry by time-of-flight (e.g., Fluidigm CyTOF), cycling of fluorochromes (e.g., Akoya Biosciences CODEX\/PhenoCycler-Fusion, Bruker Canopy, Lunaphore Comet, and CyCIF) and digital spatial profiling or transcriptomics (e.g., GeoMx or Visium, Vizgen Merscope) are being utilized to accurately assess the complex cellular network within the tissue microenvironment. In cancer research, these platforms enable characterization of immune cell phenotypes and expression of potential therapeutic targets, such as PDL-1 and CTLA-4. Newer spatial profiling platforms allow for detection of numerous protein targets, in combination with whole transcriptome analysis, in a single liver biopsy tissue section. Macrophages can also be specifically targeted and analyzed, enabling quantification of both protein and gene expression within specific cell phenotypes, including TAMs. This review describes the workflow of each platform, summarizes recent research using these approaches, and explains the advantages and limitations of each.<\/jats:p>","DOI":"10.3390\/cancers14081861","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T13:39:51Z","timestamp":1649338791000},"page":"1861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cutting-Edge Platforms for Analysis of Immune Cells in the Hepatic Microenvironment\u2014Focus on Tumor-Associated Macrophages in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9661-7165","authenticated-orcid":false,"given":"Daniel E.","family":"Millian","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A.","family":"Saldarriaga","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Wanninger","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-9074","authenticated-orcid":false,"given":"Jared K.","family":"Burks","sequence":"additional","affiliation":[{"name":"Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef N.","family":"Rafati","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Gosnell","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0645-7621","authenticated-orcid":false,"given":"Heather L.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1056\/NEJMra1713263","article-title":"Hepatocellular Carcinoma","volume":"380","author":"Villanueva","year":"2019","journal-title":"N. 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