{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:58:08Z","timestamp":1793228288969,"version":"4.5.0"},"reference-count":255,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT)","doi-asserted-by":"publisher","award":["21K06925"],"award-info":[{"award-number":["21K06925"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient\u2019s survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules.<\/jats:p>","DOI":"10.3390\/ijms25137346","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T09:50:32Z","timestamp":1720086632000},"page":"7346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression"],"prefix":"10.3390","volume":"25","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Oita University Faculty of Medicine, Yufu 879-5593, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7993-2436","authenticated-orcid":false,"given":"Jiazhou","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8544, Japan"},{"name":"Division of HTLV-1\/ATL Carcinogenesis and Therapeutics, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4944-5807","authenticated-orcid":false,"given":"Shingo","family":"Nakahata","sequence":"additional","affiliation":[{"name":"Division of HTLV-1\/ATL Carcinogenesis and Therapeutics, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0999-5636","authenticated-orcid":false,"given":"Hidekatsu","family":"Iha","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Oita University Faculty of Medicine, Yufu 879-5593, Japan"},{"name":"Division of Pathophysiology, The Research Center for GLOBAL and LOCAL Infectious Diseases (RCGLID), Oita University, Yufu 879-5593, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Arneth, B. 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