Nature Communications (Dec 2024)
Copper chelation redirects neutrophil function to enhance anti-GD2 antibody therapy in neuroblastoma
- Jourdin R. C. Rouaen,
- Antonietta Salerno,
- Tyler Shai-Hee,
- Jayne E. Murray,
- Giulia Castrogiovanni,
- Charlotte McHenry,
- Toni Rose Jue,
- Vu Pham,
- Jessica Lilian Bell,
- Ensieh Poursani,
- Emanuele Valli,
- Riccardo Cazzoli,
- Naomi Damstra,
- Delia J. Nelson,
- Kofi L. P. Stevens,
- Jonathan Chee,
- Iveta Slapetova,
- Maria Kasherman,
- Renee Whan,
- Francis Lin,
- Blake J. Cochran,
- Nicodemus Tedla,
- Feyza Colakoglu Veli,
- Aysen Yuksel,
- Chelsea Mayoh,
- Federica Saletta,
- Daniele Mercatelli,
- Tatyana Chtanova,
- Arutha Kulasinghe,
- Daniel Catchpoole,
- Giuseppe Cirillo,
- Maté Biro,
- Holger N. Lode,
- Fabio Luciani,
- Michelle Haber,
- Juliet C. Gray,
- Toby N. Trahair,
- Orazio Vittorio
Affiliations
- Jourdin R. C. Rouaen
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Antonietta Salerno
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Tyler Shai-Hee
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Jayne E. Murray
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Giulia Castrogiovanni
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Charlotte McHenry
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Toni Rose Jue
- Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney
- Vu Pham
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Jessica Lilian Bell
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Ensieh Poursani
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Emanuele Valli
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS
- Riccardo Cazzoli
- Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney
- Naomi Damstra
- Institute for Respiratory Health, National Centre for Asbestos Related Diseases, University of Western Australia
- Delia J. Nelson
- Curtin Medical School, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University
- Kofi L. P. Stevens
- Institute for Respiratory Health, National Centre for Asbestos Related Diseases, University of Western Australia
- Jonathan Chee
- Institute for Respiratory Health, National Centre for Asbestos Related Diseases, University of Western Australia
- Iveta Slapetova
- Katharina Gaus Light Microscopy Facility, University of New South Wales
- Maria Kasherman
- Katharina Gaus Light Microscopy Facility, University of New South Wales
- Renee Whan
- Katharina Gaus Light Microscopy Facility, University of New South Wales
- Francis Lin
- School of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW Sydney
- Blake J. Cochran
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Nicodemus Tedla
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Feyza Colakoglu Veli
- EMBL Australia, Single Molecule Science Node, School of Biomedical Sciences, UNSW Sydney
- Aysen Yuksel
- Tumour Bank, Children’s Hospital at Westmead
- Chelsea Mayoh
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Federica Saletta
- Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney
- Daniele Mercatelli
- Department of Pharmacy and Biotechnology, University of Bologna
- Tatyana Chtanova
- School of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW Sydney
- Arutha Kulasinghe
- Frazer Institute, University of Queensland
- Daniel Catchpoole
- Tumour Bank, Children’s Hospital at Westmead
- Giuseppe Cirillo
- Department of Pharmacy Health and Nutritional Science, University of Calabria
- Maté Biro
- EMBL Australia, Single Molecule Science Node, School of Biomedical Sciences, UNSW Sydney
- Holger N. Lode
- Department of Pediatric Hematology-Oncology, University Medicine Greifswald
- Fabio Luciani
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Michelle Haber
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Juliet C. Gray
- Centre for Cancer Immunology, University of Southampton
- Toby N. Trahair
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- Orazio Vittorio
- School of Biomedical Sciences, UNSW Medicine & Health, UNSW Sydney
- DOI
- https://doi.org/10.1038/s41467-024-54689-x
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 20
Abstract
Abstract Anti-disialoganglioside (GD2) antibody therapy has provided clinical benefit to patients with neuroblastoma however efficacy is likely impaired by the immunosuppressive tumor microenvironment. We have previously defined a link between intratumoral copper levels and immune evasion. Here, we report that adjuvant copper chelation potentiates anti-GD2 antibody therapy to confer durable tumor control in immunocompetent models of neuroblastoma. Mechanistic studies reveal copper chelation creates an immune-primed tumor microenvironment through enhanced infiltration and activity of Fc-receptor-bearing cells, specifically neutrophils which are emerging as key effectors of antibody therapy. Moreover, we report copper sequestration by neuroblastoma attenuates neutrophil function which can be successfully reversed using copper chelation to increase pro-inflammatory effector functions. Importantly, we repurpose the clinically approved copper chelating agent Cuprior as a non-toxic, efficacious immunomodulatory strategy. Collectively, our findings provide evidence for the clinical testing of Cuprior as an adjuvant to enhance the activity of anti-GD2 antibody therapy and improve outcomes for patients with neuroblastoma.
