{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T01:46:33Z","timestamp":1774575993062,"version":"3.50.1"},"reference-count":112,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine\/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.<\/jats:p>","DOI":"10.3390\/nu13124503","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T21:32:40Z","timestamp":1639690360000},"page":"4503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1551-9465","authenticated-orcid":false,"given":"Andreia","family":"Matos","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Instituto de Sa\u00fade Ambiental, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, 1250-047 Lisboa, Portugal"},{"name":"Tumour & Microenvironment Interactions Group, INEB\u2014Institute of Biomedical Engineering, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-153 Porto, Portugal"},{"name":"ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Marcos","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Instituto de Sa\u00fade Ambiental, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-5687","authenticated-orcid":false,"given":"Manuel","family":"Bicho","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Instituto de Sa\u00fade Ambiental, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, 1250-047 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-857X","authenticated-orcid":false,"given":"Ricardo","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Instituto de Sa\u00fade Ambiental, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Tumour & Microenvironment Interactions Group, INEB\u2014Institute of Biomedical Engineering, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-153 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio do Porto, 4099-001 Porto, Portugal"},{"name":"S. Martinho Hospital, 4440-004 Valongo, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ejca.2018.07.005","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018","volume":"103","author":"Ferlay","year":"2018","journal-title":"Eur. J. 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