PD-1/PD-L1抑制剂在儿童复发难治淋巴瘤中的免疫治疗进展

The immunotherapy progress of PD-1/PD-L1 inhibitors in children with refractory lymphoma

一些临床研究中显示,以程序性细胞凋亡蛋白-1(PD-1)或程序性凋亡配体-1(PD-L1)为靶点的免疫检查点抑制剂对于难治复发儿童恶性血液疾病及肿瘤有一定疗效,对难治复发霍奇金淋巴瘤、原发性纵隔B细胞淋巴瘤有一定抗肿瘤作用,儿童和青少年耐受性相对良好。PD-1/PD-L1抑制剂似乎并未增加感染率,但对于补充糖皮质激素和/或TNF-α靶向药物免疫抑制治疗者建议使用卡氏肺囊虫预防措施。与其他类型免疫检查点抑制剂、化疗药物及组蛋白脱乙酰酶抑制剂的联合应用,目前仍处于临床研究阶段。PD-1/PD-L1抑制剂的儿童使用剂量、疗程及方案还需要多中心的进一步研究,是否能够达到持久抗肿瘤作用亦需要更深入的研究。

Immune checkpoint inhibitors targeting programmed cell death protein-1(PD-1)or programmed death ligand-1(PD-L1)have shown certain efficacy in some clinical studies for refractory and recurrent children's malignant blood diseases and tumors.It has certain anti-tumor effect on refractory and recurrent Hodgkin lymphoma and primary mediastinal B-cell lymphoma,and is relatively well tolerated in children and adolescents.PD-1/PD-L1 inhibitors do not seem to increase the infection rate,but for glucocorticoid and/or TNF supplementation-αtargeted drug immunosuppressive therapy suggests the use of preventive measures against Pneumocystis carinii.The combination of PD-1/PD-L1 inhibitors with other types of immune checkpoint inhibitors,chemotherapy agents and histone deacetylase inhibitors is still in the clinical research stage.The dosage,course of treatment and scheme of PD-1/PD-L1 inhibitors for children still need further research in multiple centers.Whether they can achieve lasting antitumor effect also needs further research.