γ δ T Cell Modulation in Anticancer Treatment

The broad antimicrobial and antitumoral reactivity of Vγ9Vδ2 T cells, their ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumors and their strong cytolytic and bactericidal activities suggest their direct involvement in immune control of cancers and infections. γδ T cells can be selectively activated by naturally occurring or synthetic phosphoantigens, and drugs that enhance their accumulation into stressed cells, offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate endogenous phosphoantigens, has enabled investigators to design experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances of the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with different types of cancer.