在临床治疗中靶向程序性细胞死亡配体1(PD-L1)/程序性细胞死亡1(PD-1)途径的免疫治疗策略在治疗多种类型的癌症方面取得了显著成功。然而,由于肿瘤和个体免疫系统的异质性，PD-L1/PD-1阻断在控制许多患者的恶性肿瘤方面仍然显示出缓慢的反应率。越来越多的证据表明，抗PD-L1/抗PD-1治疗的有效反应需要建立一个完整的免疫周期。在免疫周期的任何步骤中的损伤是免疫疗法失败的最重要原因之一。免疫周期的损伤可以通过表观遗传修饰来恢复，包括重新编程肿瘤相关免疫的环境，通过增加肿瘤抗原的呈递来引发免疫反应，通过调节T细胞运输和再激活。因此，PD-L1/PD-1阻断和表观遗传药物的合理组合可能为免疫系统再训练和改善检查点阻断治疗的临床结局提供巨大潜力.
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.
PDF(Sci-hub)