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

Date

2021

Authors

Jacquelot, N.
Seillet, C.
Wang, M.
Pizzolla, A.
Liao, Y.
Hediyeh-Zadeh, S.
Grisaru-Tal, S.
Louis, C.
Huang, Q.
Schreuder, J.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

Nature Immunology, 2021; 22(7):851-864

Statement of Responsibility

Nicolas Jacquelot ... Melissa J. Davis ... et al.

Conference Name

DOI

10.1038/s41590-021-00943-z

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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Dissertation Note

Provenance

Description

Access Status

Rights

© 2021, Crown

License

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

https://doi.org/10.1038/s41590-021-00943-z

Call number

Persistent link to this record

https://hdl.handle.net/2440/134670