Interleukin-15-Cultered Dendritic Cells Enhance Anti-Tumor Gamme Delta T Cell Functions through IL-15 Secretion

Dendritic cell (DC) vaccination can be an effective post-remission therapy for acute myeloid leukemia (AML). Yet, current DC vaccines do not encompass the ideal stimulatory triggers for innate gamma delta (gamma delta) T cell anti-tumor activity. Promoting type 1 cytotoxic gamma delta T cells in patients with AML is, however, most interesting, considering these unconventional T cells are primed for rapid function and exert meaningful control over AML. In this work, we demonstrate that interleukin (IL)-15 DCs have the capacity to enhance the anti-tumoral functions of gamma delta T cells. IL-15 DCs of healthy donors and of AML patients in remission induce the upregulation of cytotoxicity-associated and co-stimulatory molecules on the gamma delta T cell surface, but not of co-inhibitory molecules, incite gamma delta T cell proliferation and stimulate their interferon-gamma production in the presence of blood cancer cells and phosphoantigens. Moreover, the innate cytotoxic capacity of gamma delta T cells is significantly enhanced upon interaction with IL-15 DCs, both towards leukemic cell lines and allogeneic primary AML blasts. Finally, we address soluble IL-15 secreted by IL-15 DCs as the main mechanism behind the IL-15 DC-mediated gamma delta T cell activation. These results indicate that the application of IL-15-secreting DC subsets could render DC-based anti-cancer vaccines more effective through, among others, the involvement of gamma delta T cells in the anti-leukemic immune response.