Balko Justin, Sun Xiaopeng, Hanna Ann, Ocampo Andres, Taylor Brandie, Marshall Jacey, Steele Julia, Axelrod Margaret, Wescott Elizabeth, Opalenik Susan, DeMichele Angela, Esserman Laura, Liu Minetta, Nanda Rita, Wolf Denise, Swigart Lamorna Brown, Hirst Gillian, Van 't Veer Laura, Xu Yaomin
Vanderbilt University Medical Center.
Washington University in St Louis.
Res Sq. 2025 Jul 7:rs.3.rs-6926989. doi: 10.21203/rs.3.rs-6926989/v1.
This study investigates the association between peripheral blood immunological features and immunotherapy response in breast cancer. We generated and analyzed RNAseq data from 546 blood samples of patients with high-risk stage II/III HER2-negative breast cancer enrolled in the I-SPY2 trial and identified peripheral immune signatures associated with tumor characteristics and immunotherapy response. Triple negative breast cancer (TNBC) patients showed higher T cell receptor (TCR) clonality and immune activation signatures. Responders to the chemotherapy + pembrolizumab regimen had high baseline TCR diversity, with TNBC responders experiencing T cell clonal expansion and activation after treatment. A logistic regression model based on immunological features before and early-on-treatment predicted response to pembrolizumab. The model was validated in an independent cohort of patients treated with dostarlimab in the neoadjuvant setting. We report the potential of peripheral blood-derived gene expression tests to predict immunotherapy benefit, guiding personalized treatment in breast cancer with a minimally invasive approach.
本研究调查了外周血免疫特征与乳腺癌免疫治疗反应之间的关联。我们生成并分析了来自I-SPY2试验中纳入的高危II/III期HER2阴性乳腺癌患者的546份血样的RNA测序数据，并确定了与肿瘤特征和免疫治疗反应相关的外周免疫特征。三阴性乳腺癌（TNBC）患者表现出更高的T细胞受体（TCR）克隆性和免疫激活特征。化疗+帕博利珠单抗方案的应答者具有较高的基线TCR多样性，TNBC应答者在治疗后经历T细胞克隆扩增和激活。基于治疗前和治疗早期免疫特征的逻辑回归模型预测了对帕博利珠单抗的反应。该模型在新辅助治疗中接受多斯塔利单抗治疗的独立患者队列中得到验证。我们报告了外周血来源的基因表达测试预测免疫治疗获益的潜力，以微创方法指导乳腺癌的个性化治疗。
