title: Role of memory T cell subsets for adoptive immunotherapy.
abstract: Adoptive transfer of primary (unmodified) or genetically engineered antigen-specific T cells has demonstrated astonishing clinical results in the treatment of infections and some malignancies. Besides the definition of optimal targets and antigen receptors, the differentiation status of transferred T cells is emerging as a crucial parameter for generating cell products with optimal efficacy and safety profiles. Long-living memory T cells subdivide into phenotypically as well as functionally different subsets (e.g. central memory, effector memory, tissue-resident memory T cells). This diversification process is crucial for effective immune protection, with probably distinct dependencies on the presence of individual subsets dependent on the disease to which the immune response is directed as well as its organ location. Adoptive T cell therapy intends to therapeutically transfer defined T cell immunity into patients. Efficacy of this approach often requires long-term maintenance of transferred cells, which depends on the presence and persistence of memory T cells. However, engraftment and survival of highly differentiated memory T cell subsets upon adoptive transfer is still difficult to achieve. Therefore, the recent observation that a distinct subset of weakly differentiated memory T cells shows all characteristics of adult tissue stem cells and can reconstitute all types of effector and memory T cell subsets, became highly relevant. We here review our current understanding of memory subset formation and T cell subset purification, and its implications for adoptive immunotherapy.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany; Focus Group "Clinical Cell Processing and Purification", Institute for Advanced Study, TUM, Munich 81675, Germany; National Center for Infection Research (DZIF), Munich 81675, Germany. Electronic address: dirk.busch@tum.de.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany; Focus Group "Clinical Cell Processing and Purification", Institute for Advanced Study, TUM, Munich 81675, Germany.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Fräßle
authors.affiliation: Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sommermeyer
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany.
authors.forename: Veit R
authors.initials: VR
authors.lastname: Buchholz
authors.affiliation: Focus Group "Clinical Cell Processing and Purification", Institute for Advanced Study, TUM, Munich 81675, Germany; Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA. Electronic address: sriddell@fredhutch.org.
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D002470:Cell Survival; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007239:Infections / Q000276:immunology / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
keywords: Adoptive T cell therapy; Clinical cell processing and purification; Memory stem cells; T cell engineering; T cell subsets