在黑色素瘤中阻断共抑制分子PD-1可激活2型天然淋巴细胞（ILC2）依赖性抗肿瘤免疫，这一成果由澳大利亚沃尔特伊丽莎霍尔医学研究所Gabrielle T. Belz、Nicolas Jacquelot研究小组经过不懈努力而取得。相关论文于2021年6月7日发表在《自然-免疫学》杂志上。

研究人员发现在人类黑色素瘤中，高 ILC2 浸润与良好的临床预后相关。ILC2s 是细胞因子粒细胞-巨噬细胞集落刺激因子的主要生产者，其通过招募并激活嗜酸性粒细胞来增强抗肿瘤反应。肿瘤浸润性ILC2 表达程序性细胞死亡蛋白-1，这阻碍了它们在肿瘤内的积累、增殖和抗肿瘤功能。通过将白介素 33 诱导的 ILC2 激活与程序性细胞死亡蛋白 1 阻断相结合可以显著增加抗肿瘤反应，并可在体内克服这种抑制作用。

综上所述，该研究发现 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的这些功能进行抗肿瘤免疫治疗的潜在方法。

据悉，ILC2对维持组织稳态至关重要。在癌症中，ILC2s 可以同时发挥促进肿瘤进展和抗肿瘤功能，但人们对其潜在机制知之甚少，也不知道它们是否与临床预后相关或针对其可以改善患者的预后。

附：英文原文

Title: Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma

Author: Nicolas Jacquelot, Cyril Seillet, Minyu Wang, Angela Pizzolla, Yang Liao, Soroor Hediyeh-zadeh, Sharon Grisaru-Tal, Cynthia Louis, Qiutong Huang, Jaring Schreuder, Fernando Souza-Fonseca-Guimaraes, Carolyn A. de Graaf, Kevin Thia, Sean Macdonald, Mary Camilleri, Kylie Luong, Shengbo Zhang, Michael Chopin, Tristan Molden-Hauer, Stephen L. Nutt, Viktor Umansky, Bogoljub Ciric, Joanna R. Groom, Paul S. Foster, Philip M. Hansbro, Andrew N. J. McKenzie, Daniel H. D. Gray, Andreas Behren, Jonathan Cebon, Eric Vivier, Ian P. Wicks, Joseph A. Trapani, Ariel Munitz, Melissa J. Davis, Wei Shi, Paul J. Neeson, Gabrielle T. Belz

Issue&Volume: 2021-06-07

Abstract: 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. Group 2 innate lymphoid cells (ILC2s) are generally considered to have pro-tumor functions. However, Belz and colleagues demonstrate that ILC2s have anti-melanoma effects due to their high production of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor in the tumor microenvironment.

DOI: 10.1038/s41590-021-00943-z

Source: https://www.nature.com/articles/s41590-021-00943-z