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

Jacquelot, N; Seillet, C; Wang, M; Pizzolla, A; Liao, Y; Hediyeh-Zadeh, S; Grisaru-Tal, S; Louis, C; Huang, Q; Schreuder, J; Souza-Fonseca-Guimaraes, F; de Graaf, CA; Thia, K; Macdonald, S; Camilleri, M; Luong, K; Zhang, S; Chopin, M; Molden-Hauer, T; Nutt, SL; Umansky, V; Ciric, B; Groom, JR; Foster, PS; Hansbro, PM; McKenzie, ANJ; Gray, DHD; Behren, A; Cebon, J; Vivier, E; Wicks, IP; Trapani, JA; Munitz, A; Davis, MJ; Shi, W; Neeson, PJ; Belz, GT

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

Jacquelot, N Seillet, C Wang, M Pizzolla, A Liao, Y Hediyeh-Zadeh, S Grisaru-Tal, S Louis, C Huang, Q Schreuder, J Souza-Fonseca-Guimaraes, F de Graaf, CA Thia, K Macdonald, S Camilleri, M Luong, K Zhang, S Chopin, M Molden-Hauer, T Nutt, SL Umansky, V Ciric, B Groom, JR Foster, PS Hansbro, PM McKenzie, ANJ Gray, DHD Behren, A Cebon, J Vivier, E Wicks, IP Trapani, JA Munitz, A Davis, MJ Shi, W Neeson, PJ Belz, GT

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Publisher:: NATURE RESEARCH
Publication Type:: Journal Article
Citation:: Nat Immunol, 2021, 22, (7), pp. 851-864
Issue Date:: 2021-07

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Field	Value	Language
dc.contributor.author	Jacquelot, N
dc.contributor.author	Seillet, C
dc.contributor.author	Wang, M
dc.contributor.author	Pizzolla, A
dc.contributor.author	Liao, Y
dc.contributor.author	Hediyeh-Zadeh, S
dc.contributor.author	Grisaru-Tal, S
dc.contributor.author	Louis, C
dc.contributor.author	Huang, Q
dc.contributor.author	Schreuder, J
dc.contributor.author	Souza-Fonseca-Guimaraes, F
dc.contributor.author	de Graaf, CA
dc.contributor.author	Thia, K
dc.contributor.author	Macdonald, S
dc.contributor.author	Camilleri, M
dc.contributor.author	Luong, K
dc.contributor.author	Zhang, S
dc.contributor.author	Chopin, M
dc.contributor.author	Molden-Hauer, T
dc.contributor.author	Nutt, SL
dc.contributor.author	Umansky, V
dc.contributor.author	Ciric, B
dc.contributor.author	Groom, JR
dc.contributor.author	Foster, PS
dc.contributor.author	Hansbro, PM
dc.contributor.author	McKenzie, ANJ
dc.contributor.author	Gray, DHD
dc.contributor.author	Behren, A
dc.contributor.author	Cebon, J
dc.contributor.author	Vivier, E
dc.contributor.author	Wicks, IP
dc.contributor.author	Trapani, JA
dc.contributor.author	Munitz, A
dc.contributor.author	Davis, MJ
dc.contributor.author	Shi, W
dc.contributor.author	Neeson, PJ
dc.contributor.author	Belz, GT
dc.date.accessioned	2022-03-29T03:15:15Z
dc.date.available	2021-04-26
dc.date.available	2022-03-29T03:15:15Z
dc.date.issued	2021-07
dc.identifier.citation	Nat Immunol, 2021, 22, (7), pp. 851-864
dc.identifier.issn	1529-2908
dc.identifier.issn	1529-2916
dc.identifier.uri	http://hdl.handle.net/10453/155659
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	NATURE RESEARCH
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	Nat Immunol
dc.relation.isbasedon	10.1038/s41590-021-00943-z
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.mesh	Animals
dc.subject.mesh	Antibodies
dc.subject.mesh	Antineoplastic Combined Chemotherapy Protocols
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Chemotaxis, Leukocyte
dc.subject.mesh	Cytotoxicity, Immunologic
dc.subject.mesh	Eosinophils
dc.subject.mesh	Female
dc.subject.mesh	Granulocyte-Macrophage Colony-Stimulating Factor
dc.subject.mesh	Humans
dc.subject.mesh	Immune Checkpoint Inhibitors
dc.subject.mesh	Interleukin-33
dc.subject.mesh	Lymphocytes
dc.subject.mesh	Male
dc.subject.mesh	Melanoma, Experimental
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Phenotype
dc.subject.mesh	Programmed Cell Death 1 Receptor
dc.subject.mesh	Skin Neoplasms
dc.subject.mesh	Eosinophils
dc.subject.mesh	Lymphocytes
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Humans
dc.subject.mesh	Melanoma, Experimental
dc.subject.mesh	Skin Neoplasms
dc.subject.mesh	Granulocyte-Macrophage Colony-Stimulating Factor
dc.subject.mesh	Antineoplastic Combined Chemotherapy Protocols
dc.subject.mesh	Antibodies
dc.subject.mesh	Chemotaxis, Leukocyte
dc.subject.mesh	Cytotoxicity, Immunologic
dc.subject.mesh	Phenotype
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Programmed Cell Death 1 Receptor
dc.subject.mesh	Interleukin-33
dc.subject.mesh	Immune Checkpoint Inhibitors
dc.title	Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.
dc.type	Journal Article
utslib.citation.volume	22
utslib.location.activity	United States
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-03-29T03:15:08Z
pubs.issue	7
pubs.publication-status	Published
pubs.volume	22
utslib.citation.issue	7

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.

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http://hdl.handle.net/10453/155659