γδ T cells in cancer immunotherapy

Abstract

γδ T cells are one of the three immune cell types that express antigen receptors. They contribute to lymphoid antitumor surveillance and bridge the gap between innate and adaptive immunity. γδ T cells have the capacity of secreting abundant cytokines and exerting potent cytotoxicity against a wide range of cancer cells. γδ T cells exhibit important roles in immune-surveillance and immune defense against tumors and have become attractive effector cells for cancer immunotherapy. γδ T cells mediate anti-tumor therapy mainly by secreting pro-apoptotic molecules and inflammatory cytokines, or through a TCR-dependent pathway. Recently, γδ T cells are making their way into clinical trials. Some clinical trials demonstrated that γδ T cell-based immunotherapy is well tolerated and efficient. Despite the advantages that could be exploited, there are obstacles have to be addressed for the development of γδ T cell immunotherapies. Future direction for immunotherapy using γδ T cells should focus on overcoming the side effects of γδ T cells and exploring better antigens that help stimulating γδ T cell expansion in vitro.

Keywords: anti-tumor; cancer treatment; immunotherapy; γδ T cells.

Figure 1. Ag presentation functions of γδ T cells

At the tumor site, human γδ T cells have the potential to take up Ags directly by trogocytosis, phagocytosis or pinocytosis and cross-present the exogenous Ag to Ag-experimented and in-experimented αβ T cells.

Figure 2. Schematic figure of anti-tumor activity of γδ T cells

1) γδ T cells secret IFN-γ and TNF-α, IL-4 and IL-10. 2) enhanced expression of Fas-L and TRAIL in γδ T cells. 3) γδ T cells express CD16 mediates Fc antibody-dependent cellular cytotoxicity (ADCC). 4) γδ T cells release perforin and granzymes for cytotoxic activity.