Back to Search
Start Over
Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.
- Source :
-
Nature immunology [Nat Immunol] 2021 Jul; Vol. 22 (7), pp. 851-864. Date of Electronic Publication: 2021 Jun 07. - Publication Year :
- 2021
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Chemotaxis, Leukocyte drug effects
Cytotoxicity, Immunologic drug effects
Eosinophils drug effects
Eosinophils immunology
Eosinophils metabolism
Female
Granulocyte-Macrophage Colony-Stimulating Factor genetics
Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Humans
Lymphocytes immunology
Lymphocytes metabolism
Male
Melanoma, Experimental genetics
Melanoma, Experimental immunology
Melanoma, Experimental metabolism
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Programmed Cell Death 1 Receptor genetics
Programmed Cell Death 1 Receptor metabolism
Skin Neoplasms genetics
Skin Neoplasms immunology
Skin Neoplasms metabolism
Mice
Antibodies pharmacology
Antineoplastic Combined Chemotherapy Protocols pharmacology
Immune Checkpoint Inhibitors pharmacology
Interleukin-33 pharmacology
Lymphocytes drug effects
Melanoma, Experimental drug therapy
Programmed Cell Death 1 Receptor antagonists & inhibitors
Skin Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 22
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34099918
- Full Text :
- https://doi.org/10.1038/s41590-021-00943-z