Abstract
Despite recent advances, the eradication of cancers still represents a challenge which justifies the exploration of additional therapeutic strategies such as immunotherapies, including adoptive cell transfers. Human peripheral Vγ9Vδ2 T cells, which constitute a major transitional immunity lymphocyte subset, represent attractive candidates because of their broad and efficient anti-tumor functions, as well as their lack of alloreactivity and easy handling. Vγ9Vδ2 T cells act like immune cell stress sensors that can, in a tightly controlled manner but through yet incompletely understood mechanisms, detect subtle changes of levels of phosphorylated metabolites of isoprenoid synthesis pathways. Consequently, various anti-tumor immunotherapeutic strategies have been proposed to enhance their reactivity and cytotoxicity, as well as to reduce the deleterious events. In this review, we expose these advances based on different strategies and their validation in preclinical models. Importantly, we next discuss advantages and limits of each approach, by highlighting the importance of the use of relevant preclinical model for evaluation of safety and efficacy. Finally, we propose novel perspectives and strategies that should be explored using these models for therapeutic improvements.
Highlights
Reviewed by: Serena Meraviglia, University of Palermo, Italy Thomas H
For the sake of clarity, we propose to focus this present review on human γδ T cell biology, and more precisely, the human Vγ9Vδ2 T cell subset, as well as their therapeutic targeting in preclinical cancer models
Pharmacological compounds that inhibit the synthesis or the degradation of PAg in mammalian cells can block, or induce, the antigenic activation of Vγ9Vδ2 T cells, respectively [13, 14]. This Self -reactive nature of Vγ9Vδ2 T cells needs to be tightly regulated by a set of various molecules [see [15] and [16], for recent reviews], such as adhesion molecules (i.e., CD54), activating (i.e., NKG2D) or inhibiting (i.e., CD94/NKG2A,) NKR (Natural Killer Receptors), FcR (Fc Receptor) (i.e., FcRγIIIA/CD16), Nectin/Nectin-like (i.e., CD226), TLR (Toll-like Receptor) (i.e., TLR4), cytokine receptors (i.e., IL-15R, IL-21R), and immune checkpoint inhibitors (i.e., PD-1, programmed cell death protein 1)
Summary
Reviewed by: Serena Meraviglia, University of Palermo, Italy Thomas H. For the sake of clarity, we propose to focus this present review on human γδ T cell biology, and more precisely, the human Vγ9Vδ2 T cell subset, as well as their therapeutic targeting in preclinical cancer models. Based on initial results indicating an altered tumor growth control in TCR δneg mice [27], several in vivo studies showed that transferred allogeneic Vγ9Vδ2 T cells can reach and infiltrate tumor site and display a strong anti-tumor activity as evidenced by significant clinical benefits (e.g., survival, tumor growth) [28, 29].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
