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Title: Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.
Austin Authors: 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
Affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
Priority Research Centres for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia
The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia
Innate Pharma Research Labs, Marseille, France
Aix Marseille University, CNRS, INSERM, CIML, Marseille, France
Centre for Inflammation, Centenary Institute, Sydney, New South Wales, Australia
School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Melbourne, Victoria, Australia
Rheumatology Unit, Royal Melbourne Hospital, Melbourne, Australia
Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia
Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA
Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Service d'Immunologie, Marseille Immunopole, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
Department of Clinical Microbiology and Immunology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
Issue Date: Jul-2021
Date: 2021-06-07
Publication information: Nature Immunology 2021; 22(7): 851-864
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.
DOI: 10.1038/s41590-021-00943-z
ORCID: 0000-0003-0282-1892
Journal: Nature Immunology
PubMed URL: 34099918
Type: Journal Article
Appears in Collections:Journal articles

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