Austin Health

Title
Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.
Publication Date
2021-07
Author(s)
Jacquelot, Nicolas
Seillet, Cyril
Wang, Minyu
Pizzolla, Angela
Liao, Yang
Hediyeh-Zadeh, Soroor
Grisaru-Tal, Sharon
Louis, Cynthia
Huang, Qiutong
Schreuder, Jaring
Souza-Fonseca-Guimaraes, Fernando
de Graaf, Carolyn A
Thia, Kevin
Macdonald, Sean
Camilleri, Mary
Luong, Kylie
Zhang, Shengbo
Chopin, Michael
Molden-Hauer, Tristan
Nutt, Stephen L
Umansky, Viktor
Ciric, Bogoljub
Groom, Joanna R
Foster, Paul S
Hansbro, Philip M
McKenzie, Andrew N J
Gray, Daniel H D
Behren, Andreas
Cebon, Jonathan S
Vivier, Eric
Wicks, Ian P
Trapani, Joseph A
Munitz, Ariel
Davis, Melissa J
Shi, Wei
Neeson, Paul J
Belz, Gabrielle T
Type of document
Journal Article
OrcId
0000-0003-0282-1892
0000-0002-0941-8679
0000-0003-2024-4144
0000-0001-7513-6779
0000-0001-8382-6358
0000-0002-7579-0006
0000-0002-1459-2604
0000-0003-3870-0590
0000-0002-0020-6637
0000-0001-5251-7835
0000-0002-4741-3035
0000-0001-9757-2512
0000-0002-8457-8242
0000-0001-7022-8287
0000-0001-7050-6822
0000-0003-1626-3019
0000-0003-4864-7033
0000-0002-2729-5887
0000-0002-9660-9587
DOI
10.1038/s41590-021-00943-z
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.
Link
Citation
Nature Immunology 2021; 22(7): 851-864
Jornal Title
Nature Immunology

Files:

NameSizeformatDescriptionLink