{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:46:58Z","timestamp":1783637218420,"version":"3.55.0"},"reference-count":281,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victorian Cancer Agency fellowship","award":["ECRF22015"],"award-info":[{"award-number":["ECRF22015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Despite recent progress in lymphoma immunotherapy, outcomes for patients with peripheral T cell lymphomas (PTCLs) remain poor. The challenge of PTCLs reflects the profound biological heterogeneity and relative rarity of this disease group and its resistance to conventional chemotherapy, as well as the formidable challenge of generating definitive clinical evidence. However, deepening insight into the immunogenomic and microenvironmental basis of PTCL has revealed diverse mechanisms of immune escape, spanning defects in antigen presentation, apoptotic signaling, adhesion, and extensive tumor microenvironmental remodeling. These vulnerabilities provide a sound rationale for novel immunotherapeutic strategies\u2014checkpoint inhibitors, CAR-T and NK cell platforms, bispecific antibodies, oncolytic viruses, and immunomodulatory agents. Early studies show encouraging but inconsistent activity, and the variability in response highlights the urgent need for biomarker-driven stratification to deliver personalized approaches and clinically meaningful efficacy. This review synthesizes the current literature on the immune dysregulation of PTCLs, as well as advances in PTCL immunotherapy, outlining the biological rationale underpinning these approaches. We discuss approaches to molecular, transcriptomic, and microenvironmental profiling with circulating biomarkers that could enable adaptive trial designs and personalized treatment strategies. Together, these developments chart a path away from empiricism and toward precision therapy in PTCLs.<\/jats:p>","DOI":"10.3390\/jpm15110560","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T10:02:13Z","timestamp":1763546533000},"page":"560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Personalized Immunotherapy for T Cell Lymphomas: From Immune Escape to Precision Therapeutics"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-8561","authenticated-orcid":false,"given":"Joshua M. L.","family":"Casan","sequence":"first","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Department of Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"},{"name":"Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2765-2244","authenticated-orcid":false,"given":"Xiao Jing","family":"Ong","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"van der Weyden","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Department of Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-2034","authenticated-orcid":false,"given":"Costas K.","family":"Yannakou","sequence":"additional","affiliation":[{"name":"Epworth HealthCare, Melbourne, VIC 3121, Australia"},{"name":"Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-7040","authenticated-orcid":false,"given":"Joe","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Criselle","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Neeson","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-2448","authenticated-orcid":false,"given":"H. Miles","family":"Prince","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Department of Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"},{"name":"Epworth HealthCare, Melbourne, VIC 3121, Australia"},{"name":"Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","first-page":"101646","article-title":"Epidemiology of mature T-cell and NK-cell neoplasms: East and west","volume":"62","author":"Kwong","year":"2025","journal-title":"Lancet Reg. Health West. 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