Department of Oncology, Nanjing Medical University, Nanjing, Jiangsu, China.
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Med Oncol. 2021 Feb 18;38(3):30. doi: 10.1007/s12032-021-01474-1.
Adoptive transfer of γδ 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 γδ T cell differentiation, proliferation and survival. In this work, we determined that IL-15 have the capacity to enhance the anti-tumoral functions of γδ T cells. IL-15 can induce the upregulation of cytotoxicity-associated molecules on the γδ T cell surface, incite γδ T cell proliferation and decrease apoptosis. Moreover, the enhanced cytotoxicity of IL-15-induced γδ T cell was dependent on the interaction of NKG2D and MICA. Most importantly, we found that IL-15-induced γδ 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 γδ T cells in clinical practice when designing novel cell-based immunotherapies against RCC.
过继转移 γδ T 细胞是一种有吸引力的细胞免疫治疗方法，可用于治疗肾细胞癌（RCC）。白细胞介素-15（IL-15）是调节 γδ T 细胞分化、增殖和存活的关键生理细胞因子。在这项工作中，我们确定 IL-15 能够增强 γδ T 细胞的抗肿瘤功能。IL-15 可以诱导 γδ T 细胞表面细胞毒性相关分子的上调，刺激 γδ T 细胞增殖并减少细胞凋亡。此外，IL-15 诱导的 γδ T 细胞的增强细胞毒性依赖于 NKG2D 和 MICA 的相互作用。最重要的是，我们发现在体内，IL-15 诱导的 γδ T 细胞有效抑制了肿瘤生长，并延长了携带 RCC 的患者来源异种移植（PDX）小鼠的存活时间。这些结果对于在设计针对 RCC 的新型细胞免疫疗法时，前瞻性地使用 γδ T 细胞具有重要意义。
