Figure 1.

Tumor targeting mechanisms of Vδ1 and Vδ2. Different γδT cells activation modes by tumor cells. The tissue resident Vδ1 T cells recognize cancer cells via their specific Vδ1 T cell receptors (TCRs), which bind Annexin A2 and lipid antigens presented by CD1. Besides, Vδ1 T cells also use NKG2D and natural cytotoxicity receptors (NCRs) such as NKp30, NKp44, and NKp46 for tumor cell recognition. Vδ2 T cells are predominant in the peripheral blood and can migrate into tumor tissues. Their specific Vδ2 TCRs recognize BTN3A1 and BTN2A1 after the isopentenyl pyrophosphate (IPP) accumulation. CD16 expressed by Vδ2 T cells can bind therapeutic antibodies to trigger Vδ2-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). In addition, both Vδ1 and Vδ2 T cells express natural killer receptors (NKRs), which recognize tumor cells by binding to MHC class I chain-related protein A and B (MICA/B), and UL16-binding proteins (ULBPs). Created with BioRender.com.