Engineering γδ T Cells: Recognizing and Activating on Their Own Way

Adoptive cell therapy (ACT) with engineered T cells has emerged as a promising strategy for the treatment of malignant tumors. Among them, there is great interest in engineered γδ T cells for ACT. With both adaptive and innate immune characteristics, γδ T cells can be activated by γδ TCRs to recognize antigens in a MHC-independent manner, or by NK receptors to recognize stress-induced molecules. The dual recognition system enables γδ T cells with unique activation and cytotoxicity profiles, which should be considered for the design of engineered γδ T cells. However, the current designs of engineered γδ T cells mostly follow the strategies that used in αβ T cells, but not making good use of the specific characteristics of γδ T cells. Therefore, it is no surprising that current engineered γδ T cells in preclinical or clinical trials have limited efficacy. In this review, we summarized the patterns of antigen recognition of γδ T cells and the features of signaling pathways for the functions of γδ T cells. This review will additionally discuss current progress in engineered γδ T cells and provide insights in the design of engineered γδ T cells based on their specific characteristics.