Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition

γδ T cells are among the first line of defense in the immune system, playing a crucial role in bridging innate and adaptive immunity. Although γδ T cells are crucial for tumor immune surveillance, the complete mechanism by which γδ T cell receptors identify molecular targets in target cells remains unknown. Target cells can produce phosphoantigens (PAgs) via the mevalonate pathway or the methylerythritol phosphate pathway. The BTN3A1-BTN2A1 complex undergoes conformational changes in its extracellular domains upon binding to PAgs, leading to Vγ9Vδ2 T cell recognition. However, the structural basis of how Vγ9Vδ2 T cells recognize changes in this complex remains elusive. This review provides a detailed overview of the historical progress and recent discoveries regarding how Vγ9Vδ2 T cells recognize and target tumor cells. We also discuss the potential of γδ T cells immunotherapy and their role as antitumor agents.