癌症免疫疗法
化学
癌细胞
小干扰RNA
癌症
免疫检查点
体内
基因沉默
作者
Tingting Gong,Yujun Cai,Fengze Sun,Jiaxin Chen,Zhongzhen Su,Xintao Shuai,Hong Shan
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2021-10-13
卷期号:9 (23): 8007-8018
摘要
Triple-negative breast cancer (TNBC) is associated with a worse prognosis and higher mortality than other breast cancers, and intensive effort has been made to develop therapies targeting TNBC. TNBC shows higher expression levels of programmed cell death ligand 1 (PD-L1) than other breast cancer types, which leads to a decrease in the killing effects of CD8+ T cells in the tumor microenvironment. Inhibitors of apoptosis proteins (IAPs) could prevent cell death through suppressing caspase activity. Here, Birinapant, an antagonist of IAPs, was found to promote the tumor infiltration of CD8+ T cells via increasing the secretion of the chemokine CXCL9. In addition, Birinapant could inhibit tumor growth via increasing the secretion of and the sensitivity to TNF-α in a TNBC xenotransplantation mouse model. Consequently, liposomes encapsulating Birinapant and siPD-L1 mediated a form of combination therapy based on two drugs to significantly increase the therapeutic effects toward TNBC.
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