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Here, we identify the transcription factor ARID3A as a tumor\u2010intrinsic regulator of this resistant state. Genetic ablation of\n                    <jats:bold>\n                      <jats:italic>ARID3A<\/jats:italic>\n                    <\/jats:bold>\n                    inflamed the tumor microenvironment, enhanced dendritic\u2010cell activation, increased antigen\u2010specific tetramer\u2010positive and total CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration with heightened cytotoxic activity, and sensitized otherwise resistant tumors to PD\u20101 blockade in vivo. Mechanistically, ARID3A restrained endogenous nucleic\u2010acid sensing and downstream type I interferon signaling, predominantly through cGAS\u2010STING with a contributory RIG\u2010I\u2010MAVS component. Through structure\u2010guided drug repurposing, we identified the clinically approved migraine agent rimegepant as an ARID3A\u2010targeting small molecule. Direct binding assays, together with binding\u2010pocket mutations (Y326A and R266A) in matched\u2010expression rescue systems, provided strong genetic evidence for on\u2010target engagement of rimegepant with ARID3A. Rimegepant phenocopied\n                    <jats:bold>\n                      <jats:italic>ARID3A<\/jats:italic>\n                    <\/jats:bold>\n                    loss, reactivated innate immune signaling, and markedly enhanced anti\u2010PD\u20101 efficacy in murine TNBC models and patient\u2010derived organoids. Collectively, our findings define an actionable ARID3A\u2010IFN axis and support clinical evaluation of rimegepant\u2010based immunotherapy combinations, particularly in ARID3A\u2010high, immune\u2010cold TNBC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202521541","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:42:09Z","timestamp":1780454529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacologic Modulation of ARID3A with Rimegepant Reactivates Type I Interferon Signaling and Sensitizes Triple\u2010Negative Breast Cancer to PD\u20101 Blockade"],"prefix":"10.1002","volume":"13","author":[{"given":"Teng","family":"Zhou","sequence":"first","affiliation":[{"name":"Phase I Unit Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology Shanghai Medical College Fudan University  Shanghai 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