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Given the crucial role of steroids in supportive care, it is imperative to develop integrated strategies that do not compromise ICB therapy effectiveness. Here, protocols of dexamethasone resembling clinical antiemesis regimens are tested in murine models of ICB\u2010resistant breast cancer. Unexpectedly, dexamethasone enhanced the efficacy of ICB in models of primary cancer and spontaneous metastasis. Dexamethasone increased the volume of blood vessels within tumors, thereby facilitating lymphocyte infiltration and intratumor distribution. Additionally, dexamethasone depleted immunosuppressive cells and potentiated the capacity of ICB to enrich tumors of antigen\u2010recognizing cytotoxic lymphocytes. Importantly, it is found that dexamethasone does not abolish the functions of antigen\u2010na\u00efve lymphocytes and has no effect on the activity of antigen\u2010experienced lymphocytes. These findings align with recent clinical guidelines and meta\u2010analyses, suggesting that dexamethasone deserves further exploration in ICB protocols to potentially benefit efficacy. Our study supports the notion that the current practice of avoiding short\u2010term glucocorticoid steroids in patients receiving ICB should be reconsidered toward enabling the use of steroids in clinical trials of new drug combinations.<\/jats:p>","DOI":"10.1002\/advs.202514261","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T18:50:43Z","timestamp":1764355843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antiemesis Corticosteroids Potentiate Checkpoint Blockade Efficacy by Normalizing the Immune Microenvironment in Metastatic Murine Breast Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9828-8203","authenticated-orcid":false,"given":"John D.","family":"Martin","sequence":"first","affiliation":[{"name":"Department of Bioengineering Graduate School of Engineering The University of Tokyo  Bunkyo Tokyo 113\u20108656 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