Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells

Background: Adoptive immunotherapy is gaining momentum to fight malignancies, whereby gamma delta T cells have received recent attention as an alternative cell source as to natural killer cells and alpha beta cells. The advent of gamma delta T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting. Methods: In this study, we explored the beneficial effect of the immunostimulatory cytokine interleukin (IL)-15 on purified gamma delta T cells and its use as a stimulatory signal in the ex vivo expansion of gamma delta T cells for adoptive transfer. The expansion protocol was validated both with immune cells of healthy individuals and acute myeloid leukemia patients. Results: We report that the addition of IL-15 to gamma delta T cell cultures results in a more activated phenotype, a higher proliferative capacity, a more pronounced T helper 1 polarization, and an increased cytotoxic capacity of gamma delta T cells. Moreover gamma delta T cell expansion starting with peripheral blood mononuclear cells from healthy individuals and acute myeloid leukemia patients is boosted in the presence of IL-15, whereby the antitumor properties of the gamma delta T cells are strengthened as well. Conclusions: Our results support the rationale to explore the use of IL-15 in clinical adoptive therapy protocols exploiting gamma delta T cells.