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Emerging evidence suggests that inflammatory programmed cell death pathways can effectively activate anti\u2010cancer immunity across various cancer types. However, studies exploring the role of these death pathways in reversing the immune desertification and providing unique therapeutic advantages in MSS\u2010CRC remain scarce. Herein, we present a strategy using iridium(III)\u2010based inducers to concurrently trigger immunogenic PANoptosis and ferroptosis, aiming to reverse the \u201cimmune desert\u201d phenotype of MSS\u2010CRC and integrate chemotherapy with immunotherapy. Upon mitochondrial accumulation, these iridium(III) compounds inhibit complex I of the electron transport chain, leading to electron leakage and excessive reactive oxygen species generation, which collectively initiate the PANoptotic and ferroptotic signaling pathways in MSS\u2010CRC. Proteomic analysis and in vivo experiments further demonstrated that\n                    <jats:bold>Ir2<\/jats:bold>\n                    can activate PANoptotic and ferroptotic pathways to counteract immune desertification in MSS\u2010CRC. Importantly, this study establishes a mechanism\u2010guided chemical design strategy whereby subtle ligand engineering within a cyclometalated Ir(III) platform governs mitochondrial accumulation, redox disruption, and subsequent induction of immunogenic cell death.\n                  <\/jats:p>","DOI":"10.1002\/anie.3918717","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:20:54Z","timestamp":1779960054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondria\u2010Targeting Iridium(III) Complexes Induce PANoptosis and Ferroptosis for Boosting Chemoimmunotherapy Against Immune\u2010Desert Colorectal Cancer"],"prefix":"10.1002","volume":"65","author":[{"given":"Xing","family":"Liu","sequence":"first","affiliation":[{"name":"The Seventh Affiliated Hospital MOE Key Laboratory of Bioinorganic and Synthetic Chemistry State Key Laboratory of Anti\u2010Infective Drug 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