Vγ9Vδ2 T cell-based immunotherapy in hematological malignancies: from bench to bedside

Many hematological malignancies consist of tumor cells that are spontaneously recognized and killed by V gamma 9V delta 2 T cells. These tumor cells generate high amounts of intracellular phosphorylated metabolites mimicking the natural ligands and display a wide range of stress-induced self-ligands that are recognized by V gamma 9V delta 2 T cells via TCR-dependent and TCR-independent mechanisms. The intrinsic features of V gamma 9V delta 2 T cells and that of tumor cells of hematological origin constitute an ideal combination from which to develop V gamma 9V delta 2 T cell-based immune interventions. In this review, we will discuss the rationale, preclinical and clinical data in favor of this therapeutic strategy and the future perspectives of its development.