Cancer immunotherapy with γδ T cells: many paths ahead of us

Abstract

γδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity.

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235. 235.

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     Not in our library

236. 236.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

237. 237.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

238. 238.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

239. 239.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

240. 240.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

241. 241.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

242. 242.

     This reference’s wording can’t be shown under the paper’s licence.

     Not in our library

Cited by papers we hold 4

• Exploiting innate immunity for cancer immunotherapy · 2023
  No notice
• γδ T cells: origin and fate, subsets, diseases and immunotherapy · 2023
  No notice
• Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma · 2022
  No notice
• Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands · 2021
  Not checked

Reads

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