Cytotoxic and Regulatory Properties of Circulating Vδ1+ γδ T Cells: A New Player on the Cell Therapy Field?

• Published in: Molecular therapy Vol. 22; no. 8; pp. 1416 - 1422
• Main Authors: Siegers, Gabrielle M, Lamb, Lawrence S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2014; Nature Publishing Group
• Subjects: Cell- and Tissue-Based Therapy - methods; Humans; Neoplasms - therapy; Receptors, Antigen, T-Cell, gamma-delta - blood; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Reviews; T-Lymphocytes - cytology
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2014.104

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.