Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Abstract

Gamma delta (γδ) T cells are the all-rounders of our immune-system with their major histocompatibility complex-unrestricted cytotoxicity, capacity to secrete immunosti-mulatory cytokines and ability to promote the generation of tumor antigen-specific CD8⁺ and CD4⁺ T cell responses. Dendritic cell (DC)-based vaccine therapy has the prospective to harness these unique features of the γδ T cells in the fight against cancer. In this review, we will discuss our current knowledge on DC-mediated γδ T cell activation and related opportunities for tumor immunologists.

Keywords: DC-mediated γδ T cell activation; cancer; dendritic cell; immunotherapy; γδ T cell.

Figure 1.

How γδ T cells can contribute to the antitumor efficacy of dendritic cell (DC)-based vaccination. It can be postulated that DC vaccination has the ability to activate γδ T cells and initiate their expansion. In turn, activated γδ T cells can (I) further stimulate vaccine and host DCs indirectly supporting sustained antitumor T-cell immunity and NK-DC crosstalk, (II) fulfil their immunomodulatory function through the secretion of pro-inflammatory cytokines regulating innate (natural killer cells) and adaptive (T cells) cellular immunity, and (III) directly kill tumor cells. Abbreviations: CTL, cytotoxic T lymphocyte; DC, dendritic cell; DNAM, DNAX accessory molecule; FASL, Fas ligand; IFN, interferon; IL, interleukin; IPP, isopentenyl pyrophosphate; NK, natural killer cells; TC, tumor cell; TCR, tumor cell; Th1, T-helper 1 cell; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand.