title: Cytotoxic and regulatory properties of circulating Vδ1+ γδ T cells: a new player on the cell therapy field?
abstract: Exploration of cancer immunotherapy strategies that incorporate γδ T cells as primary mediators of antitumor immunity are just beginning to be explored and with a primary focus on the use of manufactured phosphoantigen-stimulated Vγ9Vδ2 T cells. Increasing evidence, however, supports a critical role for Vδ1+ γδ T cells, a minor subset in peripheral blood with distinct innate recognition properties that possess powerful tumoricidal activity. They are activated by a host of ligands including stress-induced self-antigens, glycolipids presented by CD1c/d, and potentially many others that currently remain unidentified. In contrast to Vγ9Vδ2 T cells, tumor-reactive Vδ1+ T cells are not as susceptible to activation-induced cell death and can persist in the circulation for many years, potentially offering durable immunity to some cancers. In addition, specific populations of Vδ1+ T cells can also exhibit immunosuppressive and regulatory properties, a function that can also be exploited for therapeutic purposes. This review explores the biology, function, manufacturing strategies, and potential therapeutic role of Vδ1+ T cells. We also discuss clinical experience with Vδ1+ T cells in the setting of cancer, as well as the potential of and barriers to the development of Vδ1+ T cell-based adoptive cell therapy strategies.
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Siegers
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. Electronic address: lslamb@uabmc.edu.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Lamb
mesh_terms: D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000628:therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta