IL-32γ potentiates tumor immunity in melanoma.
Details
Serval ID
serval:BIB_EAB77059FBB6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IL-32γ potentiates tumor immunity in melanoma.
Journal
JCI insight
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Publication state
Published
Issued date
17/09/2020
Peer-reviewed
Oui
Volume
5
Number
18
Pages
e138772
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Myeloid cells orchestrate the antitumor immune response and influence the efficacy of immune checkpoint blockade (ICB) therapies. We and others have previously shown that IL-32 mediates DC differentiation and macrophage activation. Here, we demonstrate that IL-32 expression in human melanoma positively correlates with overall survival, response to ICB, and an immune-inflamed tumor microenvironment (TME) enriched in mature DC, M1 macrophages, and CD8+ T cells. Treatment of B16F10 murine melanomas with IL-32 increased the frequencies of activated, tumor-specific CD8+ T cells, leading to the induction of systemic tumor immunity. Our mechanistic in vivo studies revealed a potentially novel role of IL-32 in activating intratumoral DC and macrophages to act in concert to prime CD8+ T cells and recruit them into the TME through CCL5. Thereby, IL-32 treatment reduced tumor growth and rendered ICB-resistant B16F10 tumors responsive to anti-PD-1 therapy without toxicity. Furthermore, increased baseline IL-32 gene expression was associated with response to nivolumab and pembrolizumab in 2 independent cohorts of patients with melanoma, implying that IL-32 is a predictive biomarker for anti-PD-1 therapy. Collectively, this study suggests IL-32 as a potent adjuvant in immunotherapy to enhance the efficacy of ICB in patients with non-T cell-inflamed TME.
Keywords
Animals, Antibodies, Monoclonal, Humanized/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Apoptosis, Biomarkers, Tumor/genetics, Biomarkers, Tumor/metabolism, Cell Proliferation, Cohort Studies, Dendritic Cells/immunology, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Interleukins/genetics, Interleukins/metabolism, Lymphocytes/immunology, Macrophages/immunology, Male, Melanoma/drug therapy, Melanoma/immunology, Melanoma/metabolism, Melanoma/pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Nivolumab/administration & dosage, Prognosis, Survival Rate, Tumor Cells, Cultured, Tumor Microenvironment/immunology, Xenograft Model Antitumor Assays, Cancer immunotherapy, Cellular immune response, Immunology, Melanoma, Oncology
Pubmed
Web of science
Open Access
Yes
Create date
02/09/2020 9:55
Last modification date
08/08/2024 6:42