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https://hdl.handle.net/2440/134670
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Type: | Journal article |
Title: | Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma |
Author: | 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. Nutt, S.L. et al. |
Citation: | Nature Immunology, 2021; 22(7):851-864 |
Publisher: | Springer Nature |
Issue Date: | 2021 |
ISSN: | 1529-2908 1529-2916 |
Statement of Responsibility: | Nicolas Jacquelot ... Melissa J. Davis ... et al. |
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. |
Keywords: | Immunosurveillance; Innate lymphoid cells |
Rights: | © 2021, Crown |
DOI: | 10.1038/s41590-021-00943-z |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1155342 http://purl.org/au-research/grants/nhmrc/1158024 http://purl.org/au-research/grants/nhmrc/1054925 http://purl.org/au-research/grants/nhmrc/1165443 http://purl.org/au-research/grants/nhmrc/1154325 http://purl.org/au-research/grants/nhmrc/117134 http://purl.org/au-research/grants/nhmrc/1196235 http://purl.org/au-research/grants/nhmrc/1122277 http://purl.org/au-research/grants/nhmrc/1135898 http://purl.org/au-research/grants/nhmrc/1123000 |
Published version: | http://dx.doi.org/10.1038/s41590-021-00943-z |
Appears in Collections: | Medicine publications |
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