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γδ T Cells in Tumor Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1273))

Abstract

Gamma delta (γδ) T cells which combine both innate and adaptive potential have extraordinary properties. Indeed, their strong cytotoxic and pro-inflammatory activity allows them to kill a broad range of tumor cells. Several studies have demonstrated that γδ T cells are an important component of tumor-infiltrated lymphocytes in patients affected by different types of cancer. Tumor-infiltrating γδ T cells are also considered as a good prognostic marker in many studies, though the presence of these cells is associated with poor prognosis in breast and colon cancers. The tumor microenvironment seems to drive γδ T-cell differentiation toward a tumor-promoting or a tumor-controlling phenotype, which suggests that some tumor microenvironments can limit the effectiveness of γδ T cells.

The major γδ T-cell subsets in human are the Vγ9Vδ2 T cells that are specifically activated by phosphoantigens. This unique antigenic activation process operates in a framework that requires the expression of butyrophilin 3A (BTN3A) molecules. Interestingly, there is some evidence that BTN3A expression may be regulated by the tumor microenvironment. Given their strong antitumoral potential, Vγ9Vδ2 T cells are used in therapeutic approaches either by ex vivo culture and amplification, and then adoptive transfer to patients or by direct stimulation to propagate in vivo. These strategies have demonstrated promising initial results, but greater potency is needed. Combining Vγ9Vδ2 T-cell immunotherapy with systemic approaches to restore antitumor immune response in tumor microenvironment may improve efficacy.

In this chapter, we first review the basic features of γδ T cells and their roles in the tumor microenvironment and then analyze the advances about the understanding of these cells’ activation in tumors and why this represent unique challenges for therapeutics, and finally we discuss γδ T-cell-based therapeutic strategies and future perspectives of their development.

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Authors and Affiliations

  1. Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity and Cancer, Institut Paoli Calmettes, Aix Marseille Université, Marseille, France

    Caroline Imbert & Daniel Olive

  2. Immunomonitoring Platform, Institut Paoli Calmettes, Marseille, France

    Caroline Imbert & Daniel Olive

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  1. Caroline Imbert
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  2. Daniel Olive
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Correspondence to Daniel Olive .

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  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA, Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Imbert, C., Olive, D. (2020). γδ T Cells in Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1273. Springer, Cham. https://doi.org/10.1007/978-3-030-49270-0_5

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