Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy

Derek Lee; Carl J Rosenthal; Natalie E Penn; Zachary Spencer Dunn; Yang Zhou; Lili Yang

doi:10.3390/cancers14123005

Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy

Cancers (Basel). 2022 Jun 18;14(12):3005. doi: 10.3390/cancers14123005.

Authors

Derek Lee^{1

2}, Carl J Rosenthal³, Natalie E Penn¹, Zachary Spencer Dunn^{1

4}, Yang Zhou^{1

2}, Lili Yang^{1

2

5

6}

Affiliations

¹ Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
² Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
³ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
⁴ Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
⁵ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA.
⁶ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Abstract

Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored. In addition, γδ T cells can be engineered using different gene editing technologies that augment their tumor recognition abilities and antitumor functions. In this review, we outline the unique features of different subsets of human γδ T cells and their antitumor properties. We also summarize the past and the ongoing pre-clinical studies and clinical trials utilizing γδ T cell-based cancer immunotherapy.

Keywords: allogeneic cell therapy; butyrophilins (BTN); cancer immunotherapy; chimeric antigen receptor T (CAR-T) cells; gamma delta T (γδ T) cells; zoledronate (ZOL).

Publication types

Review

Grants and funding

This work was supported by a Partnering Opportunity for Translational Research Projects Award from the California Institute for Regenerative Medicine (TRAN1-12250, to L.Y.), a UCLA BSCRC Innovation Award (to L.Y.), an Ablon Scholars Award (to L.Y.), and a T32 Microbial Pathogenesis Training Grant (Ruth L. Kirschstein National Research Service Award, T32-AI007323) (to D.L.).