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Despite advances in multimodal therapy, outcomes remain poor, emphasizing the need for novel treatment strategies. Increasing evidence reveals that IBC exhibits an immunosuppressive tumor microenvironment (TME), driven by interactions among tumor cells and TME components that promote immune evasion through cytokine signaling loops, immune checkpoint overexpression, and formation of tumor emboli that shield cancer cells from immune surveillance. Recent multi\u2010omics and spatial transcriptomic studies reveal extensive immune heterogeneity, with both \u201cimmune\u2010hot\u201d and \u201cimmune\u2010cold\u201d niches influencing responses to immunotherapy. Clinical trials testing immune checkpoint inhibitors alone or combined with chemotherapy, antibody\u2013drug conjugates, or targeted therapy show early promise but remain limited by small IBC cohorts and inconsistent diagnostic criteria. Integrating immune biomarkers, including PD\u2010L1 expression, tumor mutational burden, T\u2010cell clonality, and spatial immune signatures, may improve patient stratification and therapeutic precision. This review summarizes mechanistic and clinical insights defining IBC immunobiology, highlights barriers to durable immune activation, and outlines strategies to reprogram the TME toward an immunoactive state. Advancing combination immunotherapy and adaptive clinical trial designs through global collaboration will be essential to improve outcomes for IBC patients.<\/jats:p>","DOI":"10.1002\/advs.75766","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T09:11:58Z","timestamp":1779527518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reprogramming the Immune Landscape of Inflammatory Breast Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Verena","family":"Martinez\u2010Rodriguez","sequence":"first","affiliation":[{"name":"Cancer Biology Program University of Hawai\u02bbi Cancer Center  Honolulu Hawaii USA"},{"name":"University of Hawai\u02bbi Inflammatory Breast Cancer Clinic and Research Program  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Ogata","sequence":"additional","affiliation":[{"name":"Cancer Biology 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