ctDNA与免疫治疗相关的假性进展和超进展

ctDNA and immunotherapy-related pseudoprogression and hyperprogression

以细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性死亡受体1(PD-1)及其配体PD-L1/PD-L2为主的免疫检查点抑制剂(ICI)在肿瘤免疫治疗中扮演重要角色,部分患者对该治疗反应良好,但仍有部分患者会出现非常规反应(假性进展、超进展及解离反应等),如何早期鉴别假性进展和超进展在临床中非常必要。循环肿瘤DNA(ctDNA)因其源于凋亡和/或坏死后的肿瘤细胞而成为肿瘤早期检测的有力指标。接受ICI治疗的患者中,ctDNA减少和增加可分别见于假性进展和超进展患者,给临床医生早期识别假性进展和超进展提供了可能。本文就假性进展和超进展的定义、机制及ctDNA在鉴别假性进展和超进展中的作用进行综述。

Immune checkpoint inhibitor(ICI)based on cytotoxic T lymphocyte-associated antigen 4(CTLA-4),programmed death receptor 1(PD-1)and its ligands PD-L1/PD-L2 plays an important role in tumor immunotherapy.Some patients respond well to treatment,while some patients still have unconventional reactions(pseudoprogression,hyperprogression,dissociation reactions,etc.),thus early identification of pseudoprogression and hyperprogression is very necessary for clinical practice.Circulating tumor DNA(ctDNA)is a powerful indicator of early tumor detection because it is derived from tumor cells after apoptosis and/or necrosis.In patients receiving ICI treatment,decrease and increase of ctDNA can be seen in patients with pseudoprogression and hyperprogression respectively,which provides possibility for clinicians to identify pseudoprogression and hyperprogression early.This article reviews definition and mechanism of pseudoprogression and hyperprogression and role of ctDNA in identification of pseudoprogression and hyperprogression.