Next Article in Journal
Deep Learning for the Preoperative Diagnosis of Metastatic Cervical Lymph Nodes on Contrast-Enhanced Computed ToMography in Patients with Oral Squamous Cell Carcinoma
Previous Article in Journal
TP53 Mutations as a Driver of Metastasis Signaling in Advanced Cancer Patients
Review

T-Cell Dysfunction as a Limitation of Adoptive Immunotherapy: Current Concepts and Mitigation Strategies

1
Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada
2
Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada
3
Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Michael W. Krainer
Cancers 2021, 13(4), 598; https://doi.org/10.3390/cancers13040598
Received: 30 December 2020 / Revised: 29 January 2021 / Accepted: 29 January 2021 / Published: 3 February 2021
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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.
Over the last decades, cellular immunotherapy has revealed its curative potential. However, inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death, undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer, are discussed, with an emphasis on strategies used during ex vivo manipulations to limit T-cell dysfunction. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features are key to the development of improved cellular immunotherapies. View Full-Text
Keywords: T cells; chimeric antigen receptor; transgenic T-cell receptor; tumor-infiltrating lymphocytes; exhaustion; terminal differentiation; senescence; apoptosis; adoptive cell transfer; immunotherapy T cells; chimeric antigen receptor; transgenic T-cell receptor; tumor-infiltrating lymphocytes; exhaustion; terminal differentiation; senescence; apoptosis; adoptive cell transfer; immunotherapy
Show Figures

Figure 1

MDPI and ACS Style

Janelle, V.; Delisle, J.-S. T-Cell Dysfunction as a Limitation of Adoptive Immunotherapy: Current Concepts and Mitigation Strategies. Cancers 2021, 13, 598. https://doi.org/10.3390/cancers13040598

AMA Style

Janelle V, Delisle J-S. T-Cell Dysfunction as a Limitation of Adoptive Immunotherapy: Current Concepts and Mitigation Strategies. Cancers. 2021; 13(4):598. https://doi.org/10.3390/cancers13040598

Chicago/Turabian Style

Janelle, Valérie, and Jean-Sébastien Delisle. 2021. "T-Cell Dysfunction as a Limitation of Adoptive Immunotherapy: Current Concepts and Mitigation Strategies" Cancers 13, no. 4: 598. https://doi.org/10.3390/cancers13040598

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop