IL-32γ potentiates tumor immunity in melanoma.

Gruber, Thomas; Kremenovic, Mirela; Sadozai, Hassan; Rombini, Nives; Baeriswyl, Lukas; Maibach, Fabienne; Modlin, Robert L; Gilliet, Michel; von Werdt, Diego; Hunger, Robert E.; Jafari, S. Morteza Seyed; Parisi, Giulia; Abril-Rodriguez, Gabriel; Ribas, Antoni; Schenk, Mirjam (2020). IL-32γ potentiates tumor immunity in melanoma. JCI insight, 5(18) JCI Insight 10.1172/jci.insight.138772

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gruber, Thomas; Kremenovic, Mirela; Sadozai, Hassan Ahmed; Rombini, Nives; Bäriswyl, Lukas; von Werdt, Diego; Hunger, Robert; Jafari, Morteza and Schenk, Mirjam

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2379-3708

Publisher:

JCI Insight

Language:

English

Submitter:

Mirjam Schenk

Date Deposited:

12 Nov 2020 12:00

Last Modified:

12 Nov 2020 12:05

Publisher DOI:

10.1172/jci.insight.138772

PubMed ID:

32841222

Uncontrolled Keywords:

Cancer immunotherapy Cellular immune response Immunology Melanoma Oncology

BORIS DOI:

10.7892/boris.148109

URI:

https://boris.unibe.ch/id/eprint/148109

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