Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

Acta Pharmaceutica Sinica. B
Xi ChenLing Ding

Abstract

Immunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure. Impairments in the immune cycle can be restored by epigenetic modification, including reprogramming the environment of tumor-associated immunity, eliciting an immune response by increasing the presentation of tumor antigens, and by regulating T cell trafficking and reactivation. Thus, a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.

Citations

Aug 5, 2020·Journal of Gastroenterology·Fiona TurkesNaureen Starling
Oct 9, 2020·International Journal of Molecular Sciences·Haiyan DaiJie Ma
Oct 20, 2020·Frontiers in Oncology·Chaoyue SuJianye Zhang
Nov 25, 2020·Journal of Experimental & Clinical Cancer Research : CR·Yuanliang YanZhijie Xu
Nov 12, 2020·International Journal of Molecular Sciences·Simone PatergnaniCarlotta Giorgi
Mar 2, 2021·Acta Pharmaceutica Sinica. B·Jianfeng WangYiran Huang
Mar 26, 2021·Clinical Epigenetics·Iris LodewijkJesús M Paramio
Mar 26, 2021·International Immunopharmacology·Xiaoxu Li, Wenling Zhang
Mar 9, 2021·Signal Transduction and Targeted Therapy·Chaoyue SuLiwu Fu
Dec 21, 2021·Frontiers in Cell and Developmental Biology·Fangdie YeHaowen Jiang

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NCT02936752
NCT03250962
NCT02961101
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NCT03308396
NCT02508870
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