CLIN CANCER RES:PD-1阻断和CD27活化可以协同增强CD8+T细胞抗肿瘤活性

2018-06-06 MedSci MedSci原创

PD-1免疫检查点抑制是肿瘤免疫治疗领域具有革命性的突破,但是有反应的患者比例较低,原因与活化DC细胞较少导致的T细胞不完全激活有关。DC信号可以通过CD27激动剂增强,CLIN CANCER RES近期发表了一篇文章,研究联合CD27激动性抗体是否可以增强抗PD-1/L1的疗效。

PD-1免疫检查点抑制是肿瘤免疫治疗领域具有革命性的突破,但是有反应的患者比例较低,原因与活化DC细胞较少导致的T细胞不完全激活有关。DC信号可以通过CD27激动剂增强,CLIN CANCER RES近期发表了一篇文章,研究联合CD27激动性抗体是否可以增强抗PD-1/L1的疗效。

作者在多种肿瘤模型中比较了抗PD-1/L1,CD27激动性抗体以及两种方式联合的效果。使用转录分析及流式细胞学分析研究协同作用的机制。研究结果表明,PD-1/PD-L1阻断联合CD27激动性抗体通过增强IFNγ,颗粒酶B和T-bet增加CD8+T细胞扩增及效应细胞功能。CD8+T细胞转录学分析表明联合疗法可以有效激活IL2和Myc驱动的过程。但是,两种方法单独也有显着作用。抗PD-1/L1活化细胞毒性基因表达,而CD27激活增强细胞增殖。肿瘤模型中,CD27单抗可以与抗PD-1/L1发挥协同作用增强抗肿瘤免疫。最后,作者在人CD27转基因鼠淋巴瘤模型中发现临床相关抗CD27单抗,varlilumab与PD-L1阻断会发挥相似的协同作用。

文章最后认为,接受PD-1免疫检查点抑制剂治疗的肿瘤患者可以通过PD-1阻断和CD27激动剂联合治疗增强T细胞功能,并对这一治疗策略影响CD8+T细胞活化的机制进行了阐述。

原始出处
Sarah L.Buchan,Mohannad Fallatah,et al.PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programms That Synergize for CD8+ T-Cell-Driven Antitumor Immunity.CLIN CANCER RES.May 2018 doi:10.1158/107-0432.CCR-17-3057

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    2019-05-08 zhouqu_8
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    2019-03-27 gds2009
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    2018-08-04 wshxjq
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