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HTLV-1 carriers have a lifelong asymptomatic balance between infected cells and host antiviral immunity; however, 5\u201310% of carriers lose this balance and develop ATL. Coinfection with Strongyloides promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of HTLV-1 pathogenicity. As CD4+ T cells play a central role in host immunity, the deregulation of their function and differentiation via HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs the immunological balance. Various approaches are available for treating these abnormalities; however, hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL. The patient\u2019s immune state may contribute to the treatment outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, depends on immune function, including antibody-dependent cytotoxicity. In this comprehensive review, we summarize the immunopathogenesis of HTLV-1 infection in ATL and discuss the clinical findings that should be considered when developing treatment strategies for ATL.<\/jats:p>","DOI":"10.3390\/biom13101543","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T02:54:43Z","timestamp":1697684083000},"page":"1543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia\/Lymphoma: A Comprehensive Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Shingo","family":"Nakahata","sequence":"first","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\/0000-0002-0855-8936","authenticated-orcid":false,"given":"Daniel","family":"Enriquez-Vera","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"}]},{"given":"M. Ishrat","family":"Jahan","sequence":"additional","affiliation":[{"name":"Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sugata","sequence":"additional","affiliation":[{"name":"Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-7810","authenticated-orcid":false,"given":"Yorifumi","family":"Satou","sequence":"additional","affiliation":[{"name":"Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev-immunol-042617-053222","article-title":"Human T-Cell Leukemia Virus Type 1: Persistence and Pathogenesis","volume":"36","author":"Bangham","year":"2018","journal-title":"Annu. 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