γδ T cells and cancer
Lukas Bolini, Seth B. Coffelt, Bruno Silva-Santos, David L. Wiest, Lorenzo Galluzzi
Lukas Bolini, Seth B. Coffelt, Bruno Silva-Santos, David L. Wiest, Lorenzo Galluzzi
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Review

γδ T cells and cancer

Abstract

γδ T cells are a subset of lymphoid cells that, unlike their αβ lineage counterparts, express a heterodimeric TCR that mostly operates in an MHC-independent manner. γδ T cells are abundant in barrier tissues, where they continuously monitor epithelial cells for signs of stress or damage. Thus, γδ T cells are among the first responders to pathophysiological conditions, including viral infection and oncogenesis. Human γδ T cells can be classified based on TCR γ and δ chain usage into three main subsets: (a) Vγ9+Vδ2+ cells, accounting for most circulating γδ T cells; (b) Vδ1+ cells, which are common in epithelial linings, and (c) Vδ3+ T cells, which are fairly rare but exhibit unique specificities. Moreover, both human and murine γδ T cells can assume a spectrum of states with divergent phenotypic and functional properties. Accumulating evidence demonstrates that γδ T cells can mediate robust anticancer effects or support tumor progression and resistance to therapy, depending on numerous variables, including functional state and tumor type. Here, we critically discuss the context-dependent interaction between γδ T cells and cancer, focusing on recent developments and the challenges facing current efforts to manipulate this versatile lymphocyte subset for therapeutic purposes.

Authors

Lukas Bolini, Seth B. Coffelt, Bruno Silva-Santos, David L. Wiest, Lorenzo Galluzzi

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Figure 1

Key features of major lymphoid cell compartments in mammals.

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Key features of major lymphoid cell compartments in mammals. Mammalian l...
Mammalian lymphoid cells encompass populations with an innate behavior, rapidly responding to nonspecific signal of cellular stress irrespective of antigen presentation on MHC class I molecules, such as NK cells and other innate lymphoid cell (ILC) subsets. Moreover, the mammalian immune system relies on various populations of cells mounting exquisite antigen-specific, adaptive responses associated with molecular memory, like conventional αδ T cells and B lymphocytes. Finally, multiple mammalian immune cell populations have evolved to exhibit phenotypes and/or functional traits at the interface between innate and adaptive immunity, including γδ and NK T cells. Each of these populations encompasses a spectrum of phenotypically and functionally distinct subsets that mediate highly specialized effector functions, including cellular cytotoxicity, proinflammatory or immunosuppressive cytokine secretion, antibody production, and antigen presentation. BCR, B cell receptor; TCR, T cell receptor.