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Current studies suggest that polyamine metabolism is not only a key metabolic pathway for the formation of immunosuppressive phenotypes in tumor-associated macrophages (TAMs), but it is also profoundly involved in mitochondrial quality control signaling and the energy metabolism regulation process, so it is particularly important to further investigate the role of polyamine metabolism in the tumor microenvironment (TME). In this review, by summarizing the current research progress of key enzymes and substrates of the polyamine metabolic pathway in regulating TAMs and T cells, we propose that polyamine biosynthesis can intervene in the process of mitochondrial energy metabolism by affecting mitochondrial autophagy, which, in turn, regulates macrophage polarization and T cell differentiation. Polyamine metabolism may be a key target for the interactive dialog between HCC cells and immune cells such as TAMs, so interfering with polyamine metabolism may become an important entry point to break intercellular communication, providing new research space for developing polyamine metabolism-based therapy for HCC.<\/jats:p>","DOI":"10.3390\/ijms25020996","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T11:15:01Z","timestamp":1705317301000},"page":"996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs"],"prefix":"10.3390","volume":"25","author":[{"given":"Qingqing","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-3179","authenticated-orcid":false,"given":"Yuanxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-2946","authenticated-orcid":false,"given":"Jing","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.semcancer.2014.01.004","article-title":"Virus associated malignancies: The role of viral hepatitis in hepatocellular carcinoma","volume":"26","author":"Shlomai","year":"2014","journal-title":"Semin. 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