Author:
Dai Mengyuan,Liu Miao,Yang Hua,Küçük Can,You Hua
Abstract
AbstractProgrammed cell death protein 1(PD-1) is a type of immune-inhibitory checkpoint protein, which delivers inhibitory signals to cytotoxic T cells by binding to the programmed death ligand-1 (PD-L1) displayed on the surface of cancer cells. Antibodies blocking PD-1/PD-L1 interaction have been extensively used in treatment of human malignancies and have achieved promising outcomes in recent years. However, gradual development of resistance to PD-1/PD-L1 blockade has decreased the effectiveness of this immunotherapy in cancer patients. The underlying epigenetic mechanisms need to be elucidated for application of novel strategies overcoming this immunotherapy resistance. Epigenetic aberrations contribute to cancerogenesis by promoting different hallmarks of cancer. Moreover, these alterations may lead to therapy resistance, thereby leading to poor prognosis. Recently, the epigenetic regulatory drugs have been shown to decrease the resistance to PD-1/PD-L1 inhibitors in certain cancer patients. Inhibitors of the non-coding RNAs, DNA methyltransferases, and histone deacetylases combined with PD-1/PD-L1 inhibitors have shown considerable therapeutic efficacy against carcinomas as well as blood cancers. Importantly, DNA methylation-mediated epigenetic silencing can inhibit antigen processing and presentation, which promotes cancerogenesis and aggravates resistance to PD-1/PD-L1 blockade immunotherapy. These observations altogether suggest that the combination of the epigenetic regulatory drugs with PD-1/PD-L1 inhibitors may present potential solution to the resistance caused by monotherapy with PD-1/PD-L1 inhibitors.
Funder
the University Special Innovative Research Program of the Department of Education of Guangdong Province
the National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Hematology
Cited by
12 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献