T-Cell Dysfunction as a Limitation of Adoptive Immunotherapy: Current Concepts and Mitigation Strategies
Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada
Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada
Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada
Author to whom correspondence should be addressed.
Academic Editor: Michael W. Krainer
Received: 30 December 2020
Revised: 29 January 2021
Accepted: 29 January 2021
Published: 3 February 2021
T cells are immune cells that can be used to target infections or cancers. Adoptive T-cell immunotherapy leverages these properties and/or confers new features to T cells through ex vivo manipulations prior to their use in patients. However, as a “living drug,” the function of these cells can be hampered by several built-in physiological constraints and external factors that limit their efficacy. Manipulating T cells ex vivo can impart dysfunctional features to T cells through repeated stimulations and expansion, but it also offers many opportunities to improve the therapeutic potential of these cells, including emerging interventions to prevent or reverse T-cell dysfunction developing ex vivo or after transfer in patients. This review outlines the various forms of T-cell dysfunction, emphasizes how it affects various types of T-cell immunotherapy approaches, and describes current and anticipated strategies to limit T-cell dysfunction.