{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:09:06Z","timestamp":1789711746806,"version":"4.0.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase involved in immune signaling and has been implicated in tumor-intrinsic resistance to DNA-damaging therapies. Although SYK activity has been associated with poor outcomes in triple-negative breast cancer (TNBC), its role in resistance to combined radiotherapy and immune checkpoint blockade remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SYK expression and clinical relevance were assessed across multiple breast cancer cohorts, including radiotherapy-treated datasets. Integrated transcriptomic analyses were used to characterize SYK-associated immune states. The functional effects of pharmacologic SYK inhibition were evaluated using\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays and an immunocompetent bilateral 4T1 tumor model in female BALB\/c mice treated with radiotherapy and PD-1 blockade. Treatment-associated immune remodeling was assessed by flow cytometry and transcriptomic profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across multiple cohorts, elevated SYK expression, particularly in TNBC, was associated with inferior clinical outcomes and immune dysregulation. Pharmacologic SYK inhibition enhanced tumor responses to radiotherapy and PD-1 blockade at both irradiated and distant tumor sites. These effects were accompanied by coordinated remodeling of the tumor immune microenvironment, including suppression of neutrophil-associated signatures and reductions in immunosuppressive myeloid populations, including M2-like macrophages and myeloid-derived suppressor cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Pharmacologic SYK inhibition enhances responses to radiotherapy and PD-1 blockade in preclinical TNBC models and is accompanied by remodeling of the immunosuppressive myeloid compartment. These findings support further investigation of SYK-targeted strategies to improve responses to combined radiotherapy and immune checkpoint blockade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1929236","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:39:16Z","timestamp":1789709956000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting SYK enhances responses to radiotherapy and PD-1 blockade with myeloid immune remodeling in breast cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Yiqun","family":"Han","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic","place":["Rochester, 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