γδ T cells in cancer: a small population of lymphocytes with big implications

Abstract

γδ T cells are a small population of mostly tissue‐resident lymphocytes, with both innate and adaptive properties. These unique features make them particularly attractive candidates for the development of new cellular therapy targeted against tumor development. Nevertheless, γδ T cells may play dual roles in cancer, promoting cancer development on the one hand, while participating in antitumor immunity on the other hand. In mice, γδ T‐cell subsets preferentially produce IL‐17 or IFN‐γ. While antitumor functions of murine γδ T cells can be attributed to IFN‐γ+ γδ T cells, recent studies have implicated IL‐17+ γδ T cells in tumor growth and metastasis. However, in humans, IL‐17‐producing γδ T cells are rare and most studies have attributed a protective role to γδ T cells against cancer. In this review, we will present the current knowledge and most recent findings on γδ T‐cell functions in mouse models of tumor development and human cancers. We will also discuss their potential as cellular immunotherapy against cancer.

ABCA1/ABCB1 Ratio Determines Chemo- and Immune-Sensitivity in Human Osteosarcoma

“…This result is in line with previous findings showing that Vγ9Vδ2 T-cells infiltrating the tumors may vary independently from other T-lymphocyte subsets [57]. Indeed Vγ9Vδ2 T-cells recognize different antigens and mount a different immune-response from CD4 + and CD8 + T-lymphocytes [12,14,15].…”

“…In the present work, we focused on a recently-discovered function of ABCA1, i.e., the efflux of the isoprenoid metabolite IPP that activates Vγ9Vδ2 T-cells [19], a subset of T-lymphocytes with potential killing activity against transformed cells that act also when αβ T-cell-mediated immunity is impaired [11,12,14]. Our gain-and loss-of-function experiments provided the demonstration that ABCA1 transports IPP and modulates the activity of Vγ9Vδ2 T-lymphocytes in osteosarcoma, as it does in antigen-presenting cells [19].…”

“…γδ T-cells are less than 10% of circulating T-lymphocytes, but they are abundant within the tissues [12]. For this reason, they are physiologically involved in the mucosae defense from microbial pathogens, whereas they induce a strong pro-inflammatory response [13].…”

“…γδ T-lymphocytes peculiarly recognize non-major histocompatible complex (MHC) antigens, structurally characterized by a phosphate moieties (phosphoantigens) [14]. They mount a fast immune response, with intermediate features between innate and adaptive immunity [12,15]. Different subsets of γδ T-cells, producing different cytokines, may have pro-tumor or anti-tumor effects [12,14].…”

“…They mount a fast immune response, with intermediate features between innate and adaptive immunity [12,15]. Different subsets of γδ T-cells, producing different cytokines, may have pro-tumor or anti-tumor effects [12,14]. However, it is generally recognized that a high infiltration of Vγ9Vδ2 T-cell subset is a good prognostic factor in solid tumors [16].…”