Pro-tumor γδ T Cells in Human Cancer: Polarization, Mechanisms of Action, and Implications for Therapy

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. Indeed, γδ T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poor prognosis in various solid cancers (breast, colon and pancreatic cancer), suggesting that γδ T cells also display pro-tumor activities. In this review, we outline the current evidences of γδ T cell pro-tumor functions in human cancer. We also discuss the factors that favor γδ T cell polarization toward a pro-tumoral phenotype, the characteristics and functions of such cells, and the impact of pro-tumor subsets on γδ T cell-based therapies.

Characteristics and significance of T lymphocyte subsets in peripheral blood of osteosarcoma mice

“…They link up natural and adaptive immunity and are the first line of defense. Recent studies have shown that γδ T cells participate in tumor immunity, which can not only play a cytotoxic effect to kill tumor cells, but also mediate the immune escape of tumor cells ( 17 ).…”

Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy

“…A better understanding of mechanisms of γδ T cell activation and its TCR targeting may allow us to maximize the potential of γδ T cell-based therapy. While certain subsets of γδ T cells have been selected as potential immunotherapy agents, other subsets were identified as pro-tumoral γδ T cells and have immunosuppressive roles in some cancers [ 126 , 127 ]. Peng et al showed that a dominant Vδ1 T cell population infiltrating breast tumors were associated with immunosuppressive functions by inhibiting naive and effector T cell responses and by impairing DC maturation and function [ 128 ].…”

Expression of N 6 -methyladenosine (m 6 A) regulators correlates with immune microenvironment characteristics and predicts prognosis in diffuse large cell lymphoma (DLBCL)

“…Integrating some immunological studies [40][41][42], the immunological mechanism and final effect against tumor of the top three altered lymphocytes were shown in Table 2. We can notice that alternations of immune cell infiltration caused by m 6 A risk did not always associate with anti-tumor effect.…”