表观遗传结合免疫治疗——肿瘤治疗的新策略

Epigenetic therapy combined with immunotherapy: a novel strategy for cancer therapy

表观遗传异常频繁发生于各种肿瘤,表观遗传改变可能成为肿瘤的诊断、预后和化疗敏感性的标志物。DNA甲基化、组蛋白修饰和非编码RNA能够调控许多基因的表达,且这些表观遗传学改变在一定条件下逆转,为肿瘤的治疗提供新的机遇。近年来,随着对免疫耐受机制的深入研究,针对免疫检查点的抗体应运而生,以CTLA-4、PD-1、PD-L1抗体为代表的"免疫检查点阻断治疗"取得了突出的进展。肿瘤细胞通过表观遗传调控,直接或间接下调肿瘤细胞与宿主免疫系统相互作用的关键分子的表达,影响免疫系统识别或损害免疫系统的活性。因此,表观遗传治疗结合免疫检查点阻断治疗有望获得进一步的突破。

Aberrant epigenetic changes are happened frequently in various human cancers. Epigenetic changes may serve as potential diagnostic, prognostic and therapeutic markers. DNA methylation, histone modification and noncoding RNA may regulate gene expression. It provides a new opportunity for cancer therapy that epigenetic change is reversible under certain condition. Understanding the mechanism of immune tolerance in cancer, the blockade of immune cheek- points in cancer immunotherapy is developed, including CTLA-4, PD-1 and PD-L1 antibodies. Immune checkpoint blockade has led to durable antitumor effects in patients with metastatic melanoma, non-small cell lung cancer and other tumor types. Epigenetic alterations are well-acknowledged to be used by tumor cells to impair their immunogenicity and immune recognition. The expression of key molecules in tumor cells and the host immune system regulated directly or indirectly by epigenetic regulation can affect the identification of immune system or damage the activity of immune system. Thus epigenetic therapy combined with the blockade of immune checkpoints therapy may make a breakthrough in cancer therapy.