The capability of heterogeneous γδ T cells in cancer treatment

Front Immunol. 2023 Nov 24:14:1285801. doi: 10.3389/fimmu.2023.1285801. eCollection 2023.

Abstract

γδ T cells, a specialized subset of T lymphocytes, have garnered significant attention within the realm of cancer immunotherapy. Operating at the nexus between adaptive and innate immunological paradigms, these cells showcase a profound tumor discernment repertoire, hinting at novel immunotherapeutic strategies. Significantly, these cells possess the capability to directly identify and eliminate tumor cells without reliance on HLA-antigen presentation. Furthermore, γδ T cells have the faculty to present tumor antigens to αβ T cells, amplifying their anti-tumoral efficacy.Within the diverse and heterogeneous subpopulations of γδ T cells, distinct immune functionalities emerge, manifesting either anti-tumor or pro-tumor roles within the tumor microenvironment. Grasping and strategically harnessing these heterogeneous γδ T cell cohorts is pivotal to their integration in tumor-specific immunotherapeutic modalities. The aim of this review is to describe the heterogeneity of the γδ T cell lineage and the functional plasticity it generates in the treatment of malignant tumors. This review endeavors to elucidate the intricate heterogeneity inherent to the γδ T cell lineage, the consequential functional dynamics in combating malignancies, the latest advancements from clinical trials, and the evolving landscape of γδ T cell-based oncological interventions, while addressing the challenges impeding the field.

Keywords: CAR-γδ T; T cell subsets; adoptive cell transfer therapy; cancer immunotherapy; heterogeneity; γδ T cells.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigens, Neoplasm
  • Humans
  • Immunotherapy
  • Neoplasms*
  • Receptors, Antigen, T-Cell, gamma-delta*
  • Tumor Microenvironment

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Antigens, Neoplasm

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was supported by the National Natural Science Foundation of China (81872486, PW), the National Key Research and Development Program of China (2019YFC1316101, PW), and the Natural Science Foundation of Henan Province for Excellent Young Scholars (202300410360, PW).