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Adv."],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitors show promise in the treatment of melanoma brain metastases but are limited by CD73\/adenosine axis-mediated immune evasion. Directly targeting CD73 with antibodies faces challenges due to poor blood-brain barrier permeability and metabolic regulators within the tumor microenvironment (IL-17-driven HIF-1\u03b1\/VEGF-A). To overcome these barriers, we developed a nose-to-brain delivery platform using glycerol as a mucosal penetration enhancer to codeliver anti\u2013IL-17 and anti-CD73 antibodies. Glycerol reversibly opened nasal epithelial tight junction proteins, enhancing the brain delivery of anti\u2013IL-17 and anti-CD73 antibodies by 19.4- and 17.1-fold, respectively, while minimizing systemic exposure. Critically, anti\u2013IL-17 attenuated CD73\/adenosine axis-mediated immune evasion, significantly boosting anti-CD73 targeting efficacy. Ultimately, this combination promoted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation and residency, pro-inflammatory macrophage polarization, and reduced T\n                    <jats:sub>reg<\/jats:sub>\n                    cell infiltration, thereby eliciting a strong antitumor effect. Our results establish an efficient nose-to-brain delivery platform for macromolecules and propose a therapeutic strategy for tumors using anti\u2013IL-17 to overcome TME-imposed limitations in CD73-targeted immunotherapy.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx7966","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:00:56Z","timestamp":1778695256000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Glycerol-mediated nose-to-brain codelivery of anti\u2013IL-17 and anti-CD73 antibodies enhances immunotherapy for melanoma brain metastases"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5305-6820","authenticated-orcid":true,"given":"Xuhong","family":"Yang","sequence":"first","affiliation":[{"name":"Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging &amp; Interventional Radiology, Department of Radiology, 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