黑色素瘤生物标志物预测检查点阻断剂的响应
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By LabMedica International staff writers Posted on 27 Aug 2018 |
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图片：巴氏染色的细胞样本中恶性黑色素瘤被染色后的显微图像（图片蒙Nephron惠赐）。
免疫检查点抑制剂类药物能调动免疫系统攻击癌症，近年来，这类药物的使用极大改善了晚期黑色素瘤患者的预后。这些药物阻断遏制免疫系统的检查点分子，并释放T细胞这样的免疫防护因子，以识别和攻击癌症。
联用抗细胞毒性T淋巴细胞抗原4 (CTLA-4)与抗程序性细胞死亡蛋白1 (PD-1)疗法提升了抗肿瘤免疫力，对晚期黑色素瘤患者的好处远胜单用其中任何一种疗法。目前没有办法预测对抗CTLA-4癌症免疫疗法的反应。
美国马萨诸塞州波士顿市Dana-Farber癌症研究所(www.dana-farber.org)的科学家及其同行检查了以前未治黑色素瘤患者肿瘤细胞的主要组织相容性复合体(MHC) I类与II类蛋白质表达，并建立结果与转录分析和基因组分析之间的关联以及与抗CTLA-4、抗PD-1或组合疗法的临床效果之间的关联。
181例病例中的78例(43%)观察到黑色素瘤MHC I类膜表达大部（>50%的细胞）或全部损失，科研小组发现，这种现象与HLA-A、HLA-B、HLA-C和B2M的转录抑制相关，并能预测对抗CTLA-4疗法的原发耐受性，但是预测不了对抗PD-1疗法的耐受。 181例病例中的55例(30%)观察到大于1%的细胞有黑色素瘤MHC II类膜表达，与γ干扰素(IFN-γ)和IFN-γ介导的基因特征有关，且能预测对抗PD-1疗法的反应，但是预测不了对抗CTLA-4疗法的反应。
该研究的论文发表于2018年7月18日的《科学》杂志《转化医学》分册。第一作者、病理医师Scott Rodig博士说：“我们通过观察黑色素瘤如何逃过免疫系统的检测，或许能发现一种药剂就能产生良好效果的患者，不损失药效，且病人的忍受力更好。”
作者总结说，抗CTLA-4疗法要起效需要有稳定的黑色素瘤MHC I类表达。相反，当MHC I类表达不足时，抗PD-1疗法的主要效果与已有的IFN-γ介导的免疫活化有关，它包括肿瘤特有的MHC II类表达以及先天免疫的成分。
Dana-Farber癌症研究所>>> www.dana-farber.org
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