Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Oncoimmunology. 2021 Jun 24;10(1):1943168. doi: 10.1080/2162402X.2021.1943168. eCollection 2021.
Immunity to melanoma is thought to be mainly mediated by adaptive immune cells. To what extent innate immunity, particularly innate lymphoid cells, drive the immune response and impact melanoma prognosis and therapeutic responsiveness is not well understood. In a recent article published in , we uncovered a critical role that ILC2 play in the control of melanoma. Using both complementary mouse models and human samples, we showed that ILC2-derived granulocyte macrophage-colony stimulating factor (GM-CSF) drives eosinophil tumor recruitment and activation. We found that ILC2 express PD-1 which inhibits ILC2 effector function and impairs anti-tumor responses. We further demonstrated that the combination of IL-33 and anti-PD-1 blocking antibodies improved anti-tumor responses through the expansion of splenic and tumor-infiltrating ILC2 and eosinophils. These findings have revealed an essential mechanism involving ILC2 and eosinophils necessary for anti-melanoma immunity and immunotherapy responses.
人们认为对黑色素瘤的免疫主要是由适应性免疫细胞介导的。先天免疫，特别是固有淋巴细胞（innate lymphoid cells，ILC）在多大程度上驱动免疫反应以及影响黑色素瘤的预后和治疗反应，目前还不是很清楚。在最近发表在[杂志名称]上的一篇文章中，我们揭示了 ILC2 在控制黑色素瘤方面的关键作用。我们使用互补的小鼠模型和人类样本表明，ILC2 衍生的粒细胞巨噬细胞集落刺激因子（granulocyte macrophage-colony stimulating factor，GM-CSF）驱动嗜酸性粒细胞肿瘤募集和激活。我们发现 ILC2 表达 PD-1，抑制 ILC2 的效应功能并损害抗肿瘤反应。我们进一步证明，IL-33 和抗 PD-1 阻断抗体的联合使用通过扩展脾和肿瘤浸润性 ILC2 和嗜酸性粒细胞来改善抗肿瘤反应。这些发现揭示了涉及 ILC2 和嗜酸性粒细胞的一个重要机制，这对于抗黑色素瘤免疫和免疫治疗反应是必要的。
