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

Nicolas Jacquelot (1, 2) , Cyril Seillet (1, 3) , Minyu Wang (4, 3) , Angela Pizzolla (4, 3) , Yang Liao (1, 3, 5, 6) , Soroor Hediyeh-Zadeh (1, 3) , Sharon Grisaru-Tal (7) , Cynthia Louis (1, 3) , Qiutong Huang (1, 3, 8) , Jaring Schreuder (8) , Fernando Souza-Fonseca-Guimaraes (8) , Carolyn de Graaf (1, 3) , Kevin Thia (4) , Sean Macdonald (4) , Mary Camilleri (1, 3) , Kylie Luong (1, 3) , Shengbo Zhang (1, 3) , Michael Chopin (1, 3) , Tristan Molden-Hauer (4) , Stephen Nutt (1, 3) , Viktor Umansky (9, 10) , Bogoljub Ciric (11) , Joanna Groom (1, 3) , Paul Foster (12) , Philip Hansbro (12, 13, 14) , Andrew Mckenzie (15) , Daniel Gray (1, 3) , Andreas Behren (5, 6, 3) , Jonathan Cebon (5, 6, 3, 16) , Eric Vivier (17, 18, 19) , Ian Wicks (1, 3) , Joseph Trapani (4, 3) , Ariel Munitz (7) , Melissa Davis (1, 3) , Wei Shi (1, 5, 6, 3) , Paul Neeson (3, 4) , Gabrielle Belz (1, 3, 8)

1 WEHI - The Walter and Eliza Hall Institute of Medical Research
2 Princess Margaret Cancer Centre [Toronto, Canada]
3 University of Melbourne
4 Peter MacCallum Cancer Centre [Melbourne, Australie]
5 Olivia Newton-John Cancer Research Institute [Heidelberg, VIC, Australia]
6 La Trobe University
7 TAU - Tel Aviv University
8 University of Queensland [Brisbane]
9 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
10 Ruprecht-Karls-University [Heidelberg, Germany]
11 Jefferson (Philadelphia University + Thomas Jefferson University)
12 UoN - University of Newcastle [Australia]
13 Centenary Institute [Sidney]
14 UTS - University of Technology Sydney
15 LMB - MRC Laboratory of Molecular Biology [Cambridge, UK]
16 Ludwig Institute for Cancer Research
17 CIML - Centre d'Immunologie de Marseille - Luminy
18 Innate Pharma
19 TIMONE - Hôpital de la Timone [CHU - APHM]

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.

Domains: Life Sciences [q-bio]

Nicolas Jacquelot, Cyril Seillet, Minyu Wang, Angela Pizzolla, Yang Liao, et al.. Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma. Nature Immunology, 2021, 22 (7), pp.851-864. ⟨10.1038/s41590-021-00943-z⟩. ⟨hal-03566011⟩