New insights into epigenetic regulation of resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms and therapeutic opportunities

作者全名："Dai, Mengyuan; Liu, Miao; Yang, Hua; Kucuk, Can; You, Hua"

作者地址："[Dai, Mengyuan; You, Hua] Chongqing Med Univ, Lab Excellence Syst Biomed Pediat Oncol,Dept Hema, Pediat Res Inst,Chongqing Key Lab Pediat,Minist E, Key Lab Child Dev & Disorders,Int Sci & Technol C, 136 Zhongshan Second Rd, Chongqing 401122, Peoples R China; [Liu, Miao] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA; [Yang, Hua] Foshan Univ, Sch Med, Dept Basic Med & Biomed Engn, Foshan, Peoples R China; [Kucuk, Can] Dokuz Eylul Univ, Izmir Biomed & Genome Ctr, Izmir Int Biomed & Genome Inst, Dept Med Biol, Izmir, Turkey; [Kucuk, Can] Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst, Izmir, Turkey; [Kucuk, Can] Izmir Biomed & Genome Ctr, Basic & Translat Res Program, Izmir, Turkey; [Kucuk, Can] Dokuz Eylul Univ, Fac Med, Dept Med Biol, Izmir, Turkey"

通信作者："You, H (通讯作者)，Chongqing Med Univ, Lab Excellence Syst Biomed Pediat Oncol,Dept Hema, Pediat Res Inst,Chongqing Key Lab Pediat,Minist E, Key Lab Child Dev & Disorders,Int Sci & Technol C, 136 Zhongshan Second Rd, Chongqing 401122, Peoples R China."

来源：EXPERIMENTAL HEMATOLOGY & ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000884735900002

JCR分区：Q1

影响因子：10.9

年份：2022

卷号：11

期号：1

开始页：　

结束页：　

文献类型：Review

关键词：PD-1; PD-L1; Immune checkpoints; Therapy resistance; Epigenetic regulation; DNA methyltransferase; Histone deacetylase; Non-coding RNA

摘要："Programmed 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 of PD-1/PD-L1 immunotherapy."

基金机构：National Natural Science Foundation of China [81911530169]; University Special Innovative Research Program of the Department of Education of Guangdong Province [2020KQNCX073]

基金资助正文："The work in the lab was supported by the National Natural Science Foundation of China (81911530169) and the University Special Innovative Research Program of the Department of Education of Guangdong Province (2020KQNCX073). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."