Adoptive cell therapy of patient-derived renal cell carcinoma xenograft model with IL-15-induced γδT cells

Adoptive transfer of gamma delta T cells is an attractive approach for cell-based immunotherapy in treatment of renal cell carcinoma (RCC). Interleukin-15 (IL-15) is the key physiological cytokine that regulates gamma delta T cell differentiation, proliferation and survival. In this work, we determined that IL-15 have the capacity to enhance the anti-tumoral functions of gamma delta T cells. IL-15 can induce the upregulation of cytotoxicity-associated molecules on the gamma delta T cell surface, incite gamma delta T cell proliferation and decrease apoptosis. Moreover, the enhanced cytotoxicity of IL-15-induced gamma delta T cell was dependent on the interaction of NKG2D and MICA. Most importantly, we found that IL-15-induced gamma delta T cells effectively suppressed the tumor growth in vivo and prolonged the survival time of RCC-bearing patient-derived xenograft (PDX) mice. These results are important for the prospective use of gamma delta T cells in clinical practice when designing novel cell-based immunotherapies against RCC.