Potential use of γδ T cell-based vaccines in cancer immunotherapy

Immunotherapy is a fast advancing methodology involving one of two approaches:(1) compounds targeting immune checkpoints and (2) cellular immunomodulators. The latter approach is still largely experimental and features in vitro generated, live immune effector cells, or antigen-presenting cells. gamma delta T cells are known for their efficient in vitro tumor killing activities. Consequently, many laboratories world wide are currently testing the tumor killing function of gamma delta T cells in clinical trials. Reported benefits are modest; however, these studies have demonstrated that large gamma delta T-cell infusions were well tolerated. Here, we discuss the potential of using human gamma delta T cells not as effector cells but as a novel cellular vaccine for treatment of cancer patients. Antigen-presenting gamma delta T cells do not require to home to tumor tissues but, instead, need to interact with endogenous, tumor-specific alpha beta T cells in secondary lymphoid tissues. Newly mobilized effector alpha beta T cells are then thought to overcome the immune blockade by creating proinflammatory conditions fit for effector T-cell homing to and killing of tumor cells. Immunotherapy may include tumor antigen-loaded gamma delta T cells alone or in combination with immune checkpoint inhibitors.