Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer
Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer
Abstract Despite the great improvement of patient outcomes by trastuzumab, a monoclonal antibody targeted on HER2-positive breast cancer, approximately 23% of patients with early-stage disease treated with adjuvant trastuzumab either fail to respond or experience recurrence within 10 years, highlighting the importance of identifying which HER2-positive patients would benefit from trastuzumab upfront. Efforts to identify biomarkers predictive of response to trastuzumab in initial breast tumor core biopsies have been complicated by the clinical and biological heterogeneity of HER2-positive tumors. Therefore, we identified a trastuzumab-resistant (TrR) signature that accurately predicts response to trastuzumab quantitively and qualitatively in vitro and in vivo, via repurposing transcriptome profiles in an engineered cell line model. We additionally demonstrated that our TrR signature was associated with tumor progression and capable of stratifying patient prognosis. Our study further illustrated the possible mechanism of this resistance as being less inherited cytotoxic T cell infiltration and failure to secrete Interferon-γ upon trastuzumab treatment in TrR tumors. These findings highlight the potential clinical application of TrR signature in treatment management and identifying possible immunotherapy interventions.
Riddell Geoffrey T.、Piacsek Mitchel、Tjoe Judy A.、Yin Jun、Duffin Aspen T.、Rovin Richard A.、Last Brittany、Sand Andrea、Sun Chaoyang
Translational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research InstituteTranslational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research InstituteTranslational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research Institute||Comprehensive Breast Care Center, Aurora Sinai Medical Center, Advocate Aurora HealthTranslational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research InstituteTranslational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research InstituteAurora Neuroscience Innovation Institute, Aurora St. Luke?ˉs Medical CenterTranslational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research Institute||Biorepository and Specimen Resource Center (BSRC), Advocate Aurora Health Research InstituteTranslational Oncology Research: Quest for Understanding & Exploration (TORQUE), Advocate Aurora Health Research InstituteDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
肿瘤学医学研究方法基础医学
Riddell Geoffrey T.,Piacsek Mitchel,Tjoe Judy A.,Yin Jun,Duffin Aspen T.,Rovin Richard A.,Last Brittany,Sand Andrea,Sun Chaoyang.Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2020.01.17.20017947.点此复制
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