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<p>γδT cells comprise 1-10% of circulating T cells, are further enriched in barrier tissues such as the gut and skin, and also form a critical component of lymphoid stress surveillance. γδ T cells have been gaining prominence as an alternative to αβ T cells for cancer immunotherapy. Such popularity may be attributed to multiple factors including the MHC-independent nature of γδ T activation, which differentiates them from αβ T cells and underlies their lack of alloreactivity. In this Review, we describe efforts to optimize the potential of γδ T cells as a cancer immunotherapeutic. We discuss the impact of disease burden on efficacy and the contexts in which unmodified γδ T cells have succeeded or failed to yield durable responses. Finally, we explore options for enhancing γδ T cell efficacy including combinations with other treatments and engineering strategies to capitalize on their potency.</p>

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Harnessing the potential of γδ T cells through engineering and combination treatment for cancer therapies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月22日

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  • Jonathan Fisher,
  • Yin Wu,
  • Daniel Abate-Daga,
  • Marta Barisa,
  • Lawrence Lamb

摘要

γδT cells comprise 1-10% of circulating T cells, are further enriched in barrier tissues such as the gut and skin, and also form a critical component of lymphoid stress surveillance. γδ T cells have been gaining prominence as an alternative to αβ T cells for cancer immunotherapy. Such popularity may be attributed to multiple factors including the MHC-independent nature of γδ T activation, which differentiates them from αβ T cells and underlies their lack of alloreactivity. In this Review, we describe efforts to optimize the potential of γδ T cells as a cancer immunotherapeutic. We discuss the impact of disease burden on efficacy and the contexts in which unmodified γδ T cells have succeeded or failed to yield durable responses. Finally, we explore options for enhancing γδ T cell efficacy including combinations with other treatments and engineering strategies to capitalize on their potency.