Fundamental Questions about γδT Cells

γδT cells is a minor subgroup of T lymphocytes expressing γδ-T Cell Receptor (TCR), with many subsets, dominated by Vδ2 and Vδ1. γδT cells recognize antigens independently of the context of MHC class I, MHC class II, or CD1 presenting molecules. However, this recognition requires the expression of the transmembrane Butyrophilin proteins by the presenting cells. Their activation is controlled by many surface receptors, namely, co-stimulatory receptors, cytokines receptors, NK receptors and inhibitory receptors. Once activated, γδT cells polarize into Th1, Th2, Th17, follicular T helper or Treg cells. They can play direct anti infectious and antitumor roles through perforin-granzyme molecules, FasL and Tumor-necrosis-factor Related Apoptosis Inducing Ligand (TRAIL), antibody-dependent cellular cytotoxicity and by IFN-γ and TNF-α cytokine’s release. They also exert an indirect antitumor activity by cooperating with B cells, dendritic cells, αβT cells and NK cells. Additionally, γδT cells can infiltrate solid cancers and display a selective cytolytic activity. Conversely, γδT cells might promote cancer progression either directly through IL17 and/or VEGF, or indirectly by impairing other antitumor immune cell activities. Given its complex functions, γδT cell-based immunotherapy seems efficient and well tolerated, yet needs to overcome many obstacles including those related to the tumor environment.