IL-32γ potentiates tumor immunity in melanoma

Gruber, Thomas; Kremenovic, Mirela; Sadozai, Hassan; Rombini, Nives; Baeriswyl, Lukas; Maibach, Fabienne; Modlin, Robert L.; Gilliet, Michel; Werdt, Diego von; Hunger, Robert E.; Jafari, S. Morteza Seyed; Parisi, Giulia; Abril-Rodríguez, Gabriel; Ribas, Antoni; Schenk, Mirjam

doi:10.1172/jci.insight.138772

Cited by 24 publications

(39 citation statements)

References 71 publications

(111 reference statements)

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“…To analyze their cellular composition by means of fluorescence-activated cell sorting (FACS), murine tumors were processed as previously described [ 30 ]. Briefly, the tumors were removed and mechanically dissociated and filtered twice through a 40-μM strainer (ThermoFisher, Waltham, MA, USA) to obtain a single-cell suspension.…”

Section: Methodsmentioning

confidence: 99%

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Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

Gruber

Robatel

Kremenovic

et al. 2021

Cancers

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Agents targeting the endocannabinoid system (ECS) have gained attention as potential cancer treatments. Given recent evidence that cannabinoid receptor 2 (CB2R) regulates lymphocyte development and inflammation, we performed studies on CB2R in the immune response against melanoma. Analysis of The Cancer Genome Atlas (TCGA) data revealed a strong positive correlation between CB2R expression and survival, as well as B cell infiltration in human melanoma. In a murine melanoma model, CB2R expression reduced the growth of melanoma as well as the B cell frequencies in the tumor microenvironment (TME), compared to CB2R-deficient mice. In depth analysis of tumor-infiltrating B cells using single-cell RNA sequencing suggested a less differentiated phenotype in tumors from Cb2r−/− mice. Thus, in this study, we demonstrate for the first time a protective, B cell-mediated role of CB2R in melanoma. This gained insight might assist in the development of novel, CB2R-targeted cancer therapies.

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Section: Methodsmentioning

confidence: 99%

“…We obtained previously published single-cell RNA-sequencing data on CD45 + and CD45 − FACS purified cells from human melanoma samples from GSE72056 [ 38 ]. The analysis was performed as previously described [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

Gruber

Robatel

Kremenovic

et al. 2021

Cancers

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“…Pregnant mice were randomly divided into three groups for injection of saline (n = 7), recombinant IL-32β-1 μg (n = 7) or IL-32β-3 μg (n = 7) via the tail vein on GD8.5, GD11.5, GD14.5, and GD16.5. The dosage of IL-32β was determined from the literature [31][32][33] . Blood pressure and proteinuria were measured as described in a previous study 34 .…”

Section: Pmn Adhesion Assaymentioning

confidence: 99%

“…IL-32 has nine alternatively spliced isoforms including IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32 small (sm), all of which show differences in terms of effects and potency in eliciting a specific effect 25 . The specific receptor for IL- 32 has not yet been identified. However, it has been reported that proteinase 3 (PR3) may be a binding receptor of IL-32 26,27 .…”

Section: Introductionmentioning

confidence: 99%

Placenta-derived IL-32β activates neutrophils to promote preeclampsia development

Liú

Ding

et al. 2021

Cell Mol Immunol

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Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia (PE). Neutrophils (PMNs) are activated in PE patients, but the mechanism and consequences of PMN activation need to be further explored. Here, we demonstrated that interleukin-32 (IL-32) expression was significantly upregulated in syncytiotrophoblasts (STBs) and that IL-32β was the major isoform with increased expression in the placenta of severe PE (sPE) patients. Furthermore, the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients, indicating that IL-32 in the serum is derived mainly from the placenta. Then, in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells (HUVECs) and enhance the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) in HUVECs, which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870. In addition, we showed that IL-32β mainly activated PMNs by binding to proteinase 3. Finally, IL-32β administration induced a PE-like phenotype in a pregnant mouse model. This study provides evidence of the involvement of IL-32β in the pathogenesis of PE.

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“…M2-M1 repolarization agents include CCR5 and CCR5/CCR2, as well as IL-32. Treatment of murine melanoma with IL-32 improved dendritic cell function and triggered M1 polarization as well as CCL5 release in macrophages, resulting in CCR5-mediated CD8 + T cell infiltration into the tumor microenvironment and the eradication of cancer cells [ 19 ]. IL-32 reduced tumor growth and rendered immune checkpoint inhibitor-resistant tumors responsive to anti-PD-1 therapy without toxicity.…”

Section: Is Innate Immunity Important: Yes or No?mentioning

confidence: 99%

The “Great Debate” at Melanoma Bridge 2020: December, 5th, 2020

Ascierto

Atkins²,

Eggermont

et al. 2021

J Transl Med

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The Great Debate session at the 2020 Melanoma Bridge virtual congress (December 3rd–5th, Italy) featured counterpoint views from experts on five specific controversial issues in melanoma. The debates considered whether or not innate immunity is important in the response to cancer and immunotherapy, how useful are the revised American Joint Committee on Cancer (AJCC) classification for the staging of patients, the use of sentinel node biopsy for staging patients, the use of triplet combination of targeted therapy plus immunotherapy versus combined immunotherapy, and the respective benefits of neoadjuvant versus adjuvant therapy. As is usual with Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their own personal opinion.

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IL-32γ potentiates tumor immunity in melanoma

Cited by 24 publications

References 71 publications

Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

Placenta-derived IL-32β activates neutrophils to promote preeclampsia development

The “Great Debate” at Melanoma Bridge 2020: December, 5th, 2020

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