{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:09:13Z","timestamp":1789736953847,"version":"4.0.1"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>B7-H3\/CD276 is an emerging immunotherapy target in cancers. However, limited knowledge of B7-H3 signaling and its role in modulating the tumor microenvironment hinders the clinical application of B7-H3-targeting therapy. Here, we report that B7-H3 plays dual roles in regulating myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs), thereby promoting tumor progression and therapy resistance, respectively. We comprehensively characterized a non-canonical function of B7-H3 that triggers MAPK signaling in monocytic MDSCs and induces cellular senescence. The senescent monocytic M-MDSCs secreted chemokines to recruit immunosuppressive granulocytic MDSCs. Genetic deletion or pharmacological inhibition of B7-H3\/Cd276 reduced Gr-MDSCs and delayed tumor progression. Nevertheless, the secretory factor SPINK1 derived from MDSCs compensatorily activates EGFR\/MEK\/ERK signaling in CAFs and promotes their extracellular matrix remodeling features, dampening B7-H3-targeting immunotherapy. Combining the B7-H3 monoclonal antibody with the FDA-approved MEK inhibitor trametinib showed durable anti-tumor effects in preclinical models of castration-resistant prostate cancer by fully attenuating immunosuppressive mechanisms.<\/jats:p>","DOI":"10.1158\/2159-8290.cd-25-1613","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:52:57Z","timestamp":1789735977000},"update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Functions of B7-H3-MAPK Signaling Orchestrate Tumor Immunosuppression via Regulating the Plasticity of Myeloid-derived Suppressor Cells and Fibroblasts"],"prefix":"10.1158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2236-4708","authenticated-orcid":false,"given":"Wei","family":"Shi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Texas MD Anderson Cancer 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