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

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

doi:10.1038/s41590-021-00943-z

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

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. NuttViktor 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

^*Corresponding author for this work

Clinical Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

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.

Original language	English
Pages (from-to)	851-864
Number of pages	14
Journal	Nature Immunology
Volume	22
Issue number	7
DOIs	https://doi.org/10.1038/s41590-021-00943-z
State	Published - Jul 2021

Funding

Funders	Funder number
Allergan and Compugen
Australian Government NHMRC
CRISPR Therapeutics
Cancer Biology Research Center
Cure Cancer Australia
Melbourne Research Scholarship
Reid Charitable Trusts
Richard Eimert Research Fund on Solid Tumors
Roche Genentech
Walter and Eliza Hall Institute
Israel Cancer Research Fund
Bristol-Myers Squibb
Victorian Cancer Agency
John T. Reid Charitable Trusts
Merck Sharp and Dohme
Department of Health and Human Services, State Government of Victoria
Australian Government
Medical Research Council	U105178805
Medical Research Council
National Health and Medical Research Council	1054925, 1135898, 1155342, 1122277, 1165443, 1154325, 1123000, 1113577, 1175134, 1140406, 1158024, 1196235
National Health and Medical Research Council
Cancer Council NSW	RG21-05
Cancer Council NSW
Cancer Australia	1158085, 1163990
Cancer Australia
Cure Cancer Australia Foundation	GNT1163990
Cure Cancer Australia Foundation
Deutsche Forschungsgemeinschaft	259332240/RTG 2099
Deutsche Forschungsgemeinschaft
United States-Israel Binational Science Foundation	2015163
United States-Israel Binational Science Foundation
Israel Cancer Association
Israel Science Foundation	886/15, 542/20
Israel Science Foundation
Fondation ARC pour la Recherche sur le Cancer
Tel Aviv University
State Government of Victoria
Cancer Biology Research Center, Tel Aviv University
Commonwealth Serum Laboratories

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41590-021-00943-z

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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, C. A., Thia, K., Macdonald, S., Camilleri, M., Luong, K., Zhang, S., Chopin, M., Molden-Hauer, T., ... Belz, G. T. (2021). Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma. Nature Immunology, 22(7), 851-864. https://doi.org/10.1038/s41590-021-00943-z

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, Crown.",

year = "2021",

month = jul,

doi = "10.1038/s41590-021-00943-z",

language = "אנגלית",

volume = "22",

pages = "851--864",

journal = "Nature Immunology",

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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 2021, 'Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma', Nature Immunology, vol. 22, no. 7, pp. 851-864. https://doi.org/10.1038/s41590-021-00943-z

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T1 - Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma

AU - Jacquelot, Nicolas

AU - Seillet, Cyril

AU - Wang, Minyu

AU - Pizzolla, Angela

AU - Liao, Yang

AU - Hediyeh-zadeh, Soroor

AU - Grisaru-Tal, Sharon

AU - Louis, Cynthia

AU - Huang, Qiutong

AU - Schreuder, Jaring

AU - Souza-Fonseca-Guimaraes, Fernando

AU - de Graaf, Carolyn A.

AU - Thia, Kevin

AU - Macdonald, Sean

AU - Camilleri, Mary

AU - Luong, Kylie

AU - Zhang, Shengbo

AU - Chopin, Michael

AU - Molden-Hauer, Tristan

AU - Nutt, Stephen L.

AU - Umansky, Viktor

AU - Ciric, Bogoljub

AU - Groom, Joanna R.

AU - Foster, Paul S.

AU - Hansbro, Philip M.

AU - McKenzie, Andrew N.J.

AU - Gray, Daniel H.D.

AU - Behren, Andreas

AU - Cebon, Jonathan

AU - Vivier, Eric

AU - Wicks, Ian P.

AU - Trapani, Joseph A.

AU - Munitz, Ariel

AU - Davis, Melissa J.

AU - Shi, Wei

AU - Neeson, Paul J.

AU - Belz, Gabrielle T.

PY - 2021/7

Y1 - 2021/7

N2 - 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.

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

Abstract

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UN SDGs

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