Eosinophils are attractive innate immune cells to use to potentiate T cell antitumor efficacy because they are capable of infiltrating tumors at early stages and modulating the tumor microenvironment. However, the limited number of functional eosinophils caused by the scarcity and short life of primary eosinophils in peripheral blood has greatly impeded the development of eosinophil-based immunotherapy. In this study, we established an efficient chemically defined protocol to generate a large quantity of functional eosinophils from human pluripotent stem cells (hPSCs) with nearly 100% purity expressing eosinophil peroxidase. These hPSC-derived eosinophils transcriptionally resembled their primary counterpart. Moreover, hPSC-derived eosinophils showed competent tumor killing capacity in established solid tumors. Furthermore, the combination of hPSC-derived eosinophils with CAR-T cells exhibited potential synergistic effects, inhibiting tumor growth and enhancing mouse survival. Our study opens up new avenues for the development of eosinophil-based immunotherapies to treat cancer.

嗜酸性粒细胞是有吸引力的先天免疫细胞，可用于增强 T 细胞的抗肿瘤功效，因为它们能够在早期浸润肿瘤并调节肿瘤微环境。然而，由于外周血中原发性嗜酸性粒细胞稀缺且寿命短，功能性嗜酸性粒细胞数量有限，极大地阻碍了以嗜酸性粒细胞为基础的免疫疗法的发展。在这项研究中，我们建立了一种有效的化学定义方案，从人类多能干细胞 (hPSC) 中产生大量功能性嗜酸性粒细胞，纯度接近 100%，表达嗜酸性粒细胞过氧化物酶。这些 hPSC 衍生的嗜酸性粒细胞在转录上类似于它们的主要对应物。此外，hPSC 衍生的嗜酸性粒细胞在已建立的实体瘤中显示出有效的肿瘤杀伤能力。此外，hPSC衍生的嗜酸性粒细胞与CAR-T细胞的组合表现出潜在的协同作用，抑制肿瘤生长并提高小鼠存活率。我们的研究为开发基于嗜酸性粒细胞的免疫疗法治疗癌症开辟了新途径。