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γδ T cells and the PD-1/PD-L1 axis: a love-hate relationship in the tumor microenvironment

Jian Liu1, Min Wu2, Yifan Yang1

  • 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Journal of Translational Medicine
|June 10, 2024
PubMed

Insights

Gamma delta (γδ) T cells show promise in cancer therapy but are hindered by the tumor microenvironment. Understanding the PD-1/PD-L1 axis impact on γδ T cells is crucial for improving immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Immunotherapy

Background:

  • Gamma delta (γδ) T cells possess inherent anti-cancer cytotoxicity, independent of MHC.
  • Their therapeutic potential is limited by the immunosuppressive tumor microenvironment (TME).
  • Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 blockers are established cancer therapies.

Purpose of the Study:

  • To investigate the reciprocal interaction between the PD-1/PD-L1 axis and γδ T cells in cancer.
  • To explore the potential of targeting this axis to enhance γδ T cell-based cancer immunotherapy.

Main Methods:

  • Review of existing literature on γδ T cells, TME, and PD-1/PD-L1 pathway.
  • Analysis of preclinical and clinical data regarding γδ T cell function and immune checkpoint expression.

Main Results:

  • γδ T cells infiltrate human tumors and contribute to anti-cancer immunity.
  • The PD-1/PD-L1 axis influences γδ T cell function and infiltration within the TME.
  • Limited data exists on the direct impact of PD-1/PD-L1 blockade on γδ T cells.

Conclusions:

  • Comprehending the PD-1/PD-L1 axis's effect on γδ T cells is essential for optimizing adoptive transfer therapies.
  • Targeting this axis may represent a novel strategy for combined immunotherapeutic approaches against cancer.
Keywords:
Antitumor immunotherapyImmune checkpoint inhibitors (ICIs)Immune checkpoints (ICPs)Immunosuppressive moleculesPD-1/PD-L1Tumor microenvironment (TME)γδ T cells

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