2026-10-12T16:13:53Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33920578 2026-09-18T05:39:09Z category_696 portal_316 item_type_3 month_year_09_2026

Table 2_Targeting SYK enhances responses to radiotherapy and PD-1 blockade with myeloid immune remodeling in breast cancer.xlsx Yiqun Han (841948) Qin Zhou (239082) Anna Dibbs (25070242) Shouhai Zhu (25070245) Ping Yin (54021) Kevin D. Pavelko (14884116) Haidong Dong (10052182) Kuntian Luo (4605985) Xinyi Tu (7015430) Fabrice Lucien-Matteoni (18207178) Sean S. Park (15115006) Michael P. Grams (8877947) Meng Xu-Welliver (727165) Cameron M. Callaghan (17530239) Zhenkun Lou (48473) Robert W. Mutter (14949760) Genetic Immunology myeloid reprogramming radiation therapy spleen tyrosine kinase triple-negative breast cancer tumor microenvironment Introduction<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.</p>Methods<p>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 in vitro 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.</p>Results<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.</p>Discussion<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.</p> 2026-09-18T05:39:09Z Dataset Dataset 10.3389/fimmu.2026.1929236.s001 https://figshare.com/articles/dataset/Table_2_Targeting_SYK_enhances_responses_to_radiotherapy_and_PD-1_blockade_with_myeloid_immune_remodeling_in_breast_cancer_xlsx/33920578 CC BY 4.0