Group 2 innate lymphoid cells (ILC2s) are essential to maintain tissue homeostasis. In cancer, ILC2s can harbor both pro-tumorigenic and anti-tumorigenic functions, but we know little about their underlying mechanisms or whether they could be clinically relevant or targeted to improve patient outcomes. Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis. ILC2s are critical producers of the cytokine granulocyte-macrophage colony-stimulating factor, which coordinates the recruitment and activation of eosinophils to enhance antitumor responses. Tumor-infiltrating ILC2s expressed programmed cell death protein-1, which limited their intratumoral accumulation, proliferation and antitumor effector functions. This inhibition could be overcome in vivo by combining interleukin-33-driven ILC2 activation with programmed cell death protein-1 blockade to significantly increase antitumor responses. Together, our results identified ILC2s as a critical immune cell type involved in melanoma immunity and revealed a potential synergistic approach to harness ILC2 function for antitumor immunotherapies.

第 2 组先天淋巴细胞 (ILC2) 对于维持组织稳态至关重要。在癌症中，ILC2 可以同时具有促肿瘤和抗肿瘤功能，但我们对其潜在机制或它们是否具有临床相关性或有针对性地改善患者预后知之甚少。在这里，我们发现人类黑色素瘤中的高 ILC2 浸润与良好的临床预后相关。 ILC2 是细胞因子粒细胞-巨噬细胞集落刺激因子的关键产生者，该因子协调嗜酸性粒细胞的募集和激活以增强抗肿瘤反应。肿瘤浸润的ILC2表达程序性细胞死亡蛋白1，这限制了它们在瘤内的积累、增殖和抗肿瘤效应功能。通过将白细胞介素 33 驱动的 ILC2 激活与程序性细胞死亡蛋白 1 阻断相结合，可以在体内克服这种抑制，从而显着增加抗肿瘤反应。总之，我们的结果确定了 ILC2 是参与黑色素瘤免疫的关键免疫细胞类型，并揭示了利用 ILC2 功能进行抗肿瘤免疫治疗的潜在协​​同方法。