Plasticity of γδ T Cells: Impact on the Anti-Tumor Response

Abstract

The tumor immune microenvironment contributes to tumor initiation, progression, and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of γ and δ chains (γδ T cells) are of particular interest. γδ T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary, and prostate cancer) directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating γδ T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that γδ T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating γδ T cells could exert an immunosuppressive activity by negatively regulating dendritic cell maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to γδ T cells and promote their differentiation into γδ T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of γδ T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying γδ T cell expansion, differentiation, and recruitment in the tumor microenvironment.

Insights into Local Tumor Microenvironment Immune Factors Associated with Regression of Cutaneous Melanoma Metastases by Mycobacterium bovis Bacille Calmette–Guérin

“…These data suggest that IL-BCG treatment could attract γδ T cells to the injection sites through the CXCL9/10/11–CXCR3 chemotaxis axis. Consistent with the attraction of γδ T cells, IL-BCG also elicits a significant elevation of signature cytokines from γδ T cells, including IFNγ (42, 43), TNFα, TNFβ, and IL-15 (44) (Figure 2C; Table 2). …”

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

“…This has been clearly demonstrated in murine models of spontaneous (48), chemically induced (49), transgenic (50), and transplantable tumors (51,52). However, it seems that the activity of g/d T cells in response to tumors can differ radically according to tumor types or tumor environments (53,54). This may reflect the high diversity of the g/d T cell compartment highlighted in this study.…”

Proportions of blood-borne Vδ1+ and Vδ2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab

“…Taken together, several studies indicate that γδ T-cells can induce and facilitate both pro- and anti-tumor immune responses (47). Studies focusing on a tentative functional link between γδ T-cells and the mode of action of ipilimumab are urgently required.…”