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γδ T cells as critical anti-tumor immune effectors

Nature Cancer (2024)Cite this article

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Abstract

While the effector cells that mediate anti-tumor immunity have historically been attributed to αβ T cells and natural killer cells, γδ T cells are now being recognized as a complementary mechanism mediating tumor rejection. γδ T cells possess a host of functions ranging from antigen presentation to regulatory function and, importantly, have critical roles in eliciting anti-tumor responses where other immune effectors may be rendered ineffective. Recent discoveries have elucidated how these differing functions are mediated by γδ T cells with specific T cell receptors and spatial distribution. Their relative resistance to mechanisms of dysfunction like T cell exhaustion has spurred the development of therapeutic approaches exploiting γδ T cells, and an improved understanding of these cells should enable more effective immunotherapies.

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Fig. 1: Protumoral and anti-tumoral roles of γδ T cells.
Fig. 2: Pathways regulating γδ T cell ligand expression.
Fig. 3: Immune checkpoint expression related to the function of tumor-infiltrating γδ T cells.
Fig. 4: Approaches to current challenges and desired outcomes.

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Acknowledgements

L.F. is supported by NCI R35CA253175, Peter Michael Foundation, and the Prostate Cancer Foundation.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Marcel Arias-Badia, Ryan Chang & Lawrence Fong

  2. Immunotherapy Integrated Research Center, Fred Hutchison Cancer Center, Seattle, WA, USA

    Lawrence Fong

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  1. Marcel Arias-Badia
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Correspondence to Lawrence Fong.

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L.F. reports research support to the institution from AbbVie, Bavarian Nordic, Bristol Myers Squibb, Dendreon, Janssen, Merck and Roche–Genentech and ownership interests in Actym, Atreca, BioAtla, Bolt, ImmunoGenesis, Nutcracker, RAPT, Scribe and Senti, unrelated to the work here. The other authors declare no competing interests.

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Arias-Badia, M., Chang, R. & Fong, L. γδ T cells as critical anti-tumor immune effectors. Nat Cancer (2024). https://doi.org/10.1038/s43018-024-00798-x

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