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Adv."],"published-print":{"date-parts":[[2026,4,10]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitors (ICIs) can essentially treat cancer but only in a small subset of patients. Treatment strategies capable of effectively and robustly sensitizing refractory patients to ICIs represent a highly coveted yet unmet clinical need. In this study, we identified DJ-1 as a negative T cell regulator. DJ-1 knockout boosts antitumor immunity and significantly potentiates PD-1 and TIM-3 blockades in murine cancer models. Single-cell sequencing of tumor-infiltrating CD45\n                    <jats:sup>+<\/jats:sup>\n                    cells revealed that DJ-1 deficiency indirectly activates T cells by reprogramming macrophages. Mechanistically, loss of DJ-1 increases reactive oxygen species (ROS) in macrophages, activating NF-\u03baB\/STAT3 signaling to promote differentiation into Cxcl9\n                    <jats:sup>+<\/jats:sup>\n                    immune-stimulatory phenotypes while reducing immune-suppressive Spp1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages. Notably, this reprogramming may be stable across tumor microenvironments because the transplanted DJ-1\u2013deficient macrophages maintain T cell\u2013activating capacity. Pharmacological inhibition of DJ-1 by disulfiram markedly potentiated antitumor efficacy of PD-1 blockade. This designates DJ-1 as a promising target for overcoming immune checkpoint resistance and optimize combination therapies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady7556","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:00:23Z","timestamp":1775671223000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["DJ-1 inhibition reshapes tumor microenvironment and potentiates immune checkpoint inhibitors"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4437-0998","authenticated-orcid":true,"given":"Haiying","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 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