Efficacious and accessible sources of natural killer (NK) cells would widen their use as immunotherapeutics, particularly for solid cancers. Here, we show that human somatic cells can be directly reprogrammed into NK cells with a CD56^brightCD16^bright phenotype using pluripotency transcription factors and an optimized reprogramming medium. The directly reprogrammed NK cells have strong innate–adaptive immunomodulatory activity and are highly potent against a wide range of cancer cells, including difficult-to-treat solid cancers and cancer stem cells. Both directly reprogrammed NK cells bearing a cancer-specific chimeric antigen receptor and reprogrammed NK cells in combination with antibodies competent for antibody-dependent cell-mediated cytotoxicity led to selective anticancer effects with augmented potency. The direct reprogramming of human somatic cells into NK cells is amenable to the production of autologous and allogeneic NK cells, and will facilitate the design and testing of cancer immunotherapies and combination therapies.

自然杀伤 (NK) 细胞的有效且可获得的来源将扩大其作为免疫治疗剂的用途，特别是对于实体癌。在这里，我们展示了人类体细胞可以直接重编程为具有 CD56^亮CD16^{亮的 NK 细胞}使用多能性转录因子和优化的重编程培养基的表型。直接重编程的 NK 细胞具有很强的先天适应性免疫调节活性，并且对多种癌细胞具有很强的抵抗力，包括难以治疗的实体癌和癌症干细胞。直接重编程带有癌症特异性嵌合抗原受体的 NK 细胞和重编程的 NK 细胞与具有抗体依赖性细胞介导的细胞毒性的抗体组合导致选择性抗癌作用增强效力。将人类体细胞直接重编程为 NK 细胞有助于产生自体和同种异体 NK 细胞，并将促进癌症免疫疗法和联合疗法的设计和测试。