Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA.
Oncoimmunology. 2023 Mar 22;12(1):2175517. doi: 10.1080/2162402X.2023.2175517. eCollection 2023.
Infusion of natural killer (NK) cells is an attractive therapeutic modality in patients with cancer. However, the activity of NK cells is regulated by several mechanisms operating within solid tumors. Regulatory T (Treg) cells suppress NK cell activity through various mechanisms including deprivation of IL-2 via the IL-2 receptor alpha (CD25). Here, we investigate CD25 expression on NK cells to confer persistence in Treg cells containing solid tumor models of renal cell carcinoma (RCC). Compared with IL-2, stimulation with IL-15 increases the expression of CD25 resulting in enhanced response to IL-2 as evidenced by increased phosphorylation of STAT5. Compared with CD25 NK cells, CD25 NK cells isolated from IL-15 primed NK cells display increased proliferative and metabolic activity as well as increased ability to persist in Treg cells containing RCC tumor spheroids. These results support strategies to enrich for or selectively expand CD25 NK cells for adoptive cellular therapy of NK cells.
自然杀伤 (NK) 细胞输注是癌症患者一种有吸引力的治疗方式。然而，NK 细胞的活性受到实体瘤内多种机制的调节。调节性 T (Treg) 细胞通过多种机制抑制 NK 细胞的活性，包括通过白细胞介素 2 受体 alpha (CD25)剥夺白细胞介素 2 (IL-2)。在这里，我们研究了 NK 细胞上 CD25 的表达，以赋予其在包含肾细胞癌 (RCC) 实体瘤模型的 Treg 细胞中的持久性。与 IL-2 相比，IL-15 刺激会增加 CD25 的表达，从而导致对 IL-2 的反应增强，这表现在 STAT5 的磷酸化增加。与 CD25 NK 细胞相比，从 IL-15 预刺激的 NK 细胞中分离出的 CD25 NK 细胞显示出更高的增殖和代谢活性，以及在包含 RCC 肿瘤球体的 Treg 细胞中更持久的能力。这些结果支持了富集或选择性扩增 CD25 NK 细胞以用于 NK 细胞过继细胞治疗的策略。
