Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Drug Discov Today. 2020 Sep;25(9):1762-1771. doi: 10.1016/j.drudis.2020.07.006. Epub 2020 Jul 11.
Despite extensive research into adjuvant and neoadjuvant chemotherapy, triple-negative breast cancer (TNBC) remains a common breast cancer (BC) subtype with poor prognosis. Given that it has higher immune cell infiltration, theoretically, it should be a protagonist of potential BC immunotherapies. However, only mild responses have been observed in monotherapy with anti-programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) antibodies. In this review, we reappraise PD-1/PD-L1 inhibitor combination immunotherapy and effective experimental compounds, focusing the level of PD-L1 expression, neoantigens, abnormal signaling pathways, and tumor microenvironment signatures, to provide guidance for future clinical trials based on the molecular mechanisms involved.
尽管已经对辅助和新辅助化疗进行了广泛的研究,但三阴性乳腺癌 (TNBC) 仍然是一种预后不良的常见乳腺癌 (BC) 亚型。鉴于其具有更高的免疫细胞浸润,从理论上讲,它应该是潜在的 BC 免疫疗法的主角。然而,抗程序性死亡受体-1/程序性死亡配体-1 (PD-1/PD-L1) 抗体单药治疗仅观察到轻微反应。在这篇综述中,我们重新评估了 PD-1/PD-L1 抑制剂联合免疫疗法和有效的实验化合物,重点关注 PD-L1 表达、新抗原、异常信号通路和肿瘤微环境特征的水平,为未来的临床试验提供基于相关分子机制的指导。