{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:42:39Z","timestamp":1781138559910,"version":"3.54.1"},"reference-count":272,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["153132"],"award-info":[{"award-number":["153132"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["202403"],"award-info":[{"award-number":["202403"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Canadian Cancer Society","award":["705290"],"award-info":[{"award-number":["705290"]}]},{"DOI":"10.13039\/100020797","name":"NanoMedicines Innovation Network","doi-asserted-by":"crossref","award":["DRG 03190"],"award-info":[{"award-number":["DRG 03190"]}],"id":[{"id":"10.13039\/100020797","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Copper (Cu) is an essential element required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key immunoregulatory pathways, including those involved in inflammation, cell death, and immune evasion. Notably, Cu can drive expression of programmed death ligand 1 (PD-L1), contributing to immunosuppression, while also promoting immunogenic cell death, which stimulates adaptive immune responses. These dual effects highlight the complexity and therapeutic potential of Cu-based interventions, particularly in the context of immune modulation and toxicity. This review argues that Cu-based nanomedicines can selectively deliver high concentrations of bioactive Cu to tumor cells, inducing cell death and triggering adaptive immune responses. We summarize current knowledge on Cu\u2019s roles in cancer and immunity, emphasizing recent insights into how these intersect through Cu-mediated modulation of anticancer immune pathways. Finally, we explore the clinical potential of Cu-based nanomedicines to convert immunologically \u201ccold\u201d tumors into \u201chot\u201d ones, thereby improving responses to immunotherapy. Realizing this potential will depend on the thoughtful integration of Cu delivery approaches with existing immunotherapeutic strategies.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010075","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-1210","authenticated-orcid":false,"given":"Devon","family":"Heroux","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC V5Z 0B4, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada"},{"name":"Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC V5Z 0B4, Canada"},{"name":"Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynab","family":"Nosrati","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC V5Z 0B4, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada"},{"name":"Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel B.","family":"Bally","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, BC V5Z 0B4, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada"},{"name":"Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s42004-020-00341-w","article-title":"Open questions on the biological roles of first-row transition metals","volume":"3","author":"Crans","year":"2020","journal-title":"Commun. 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