Kim Hyojin, Chung Jin-Haeng
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
J Pathol Transl Med. 2019 Jul;53(4):199-206. doi: 10.4132/jptm.2019.04.24. Epub 2019 May 2.
Blockade of the programmed cell death-1 (PD-1) axis has already been established as an effective treatment of non-small cell lung cancer. Immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) protein is the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer. Because each PD-1/PD-L1 blockade was approved together with a specific PD-L1 IHC assay used in the clinical trials, pathologists have been challenged with performing various assays with a limited sample. To provide a more unified understanding of this, several cross-validation studies between platforms have been performed and showed consistent results. However, the interchangeability of assays may be limited in practice because of the risk of misclassification of patients for the treatment. Furthermore, several issues, including the temporal and spatial heterogeneity of PD-L1 expression in the tumor, and the potential for cytology specimens to be used as an alternative to tissue samples for PD-L1 testing, have still not been resolved. In the future, one of the main aims of immunotherapy research should be to find a novel predictive biomarker for PD-1 blockade therapy and a way to combine it with PD-L1 IHC and other tests.
程序性细胞死亡蛋白1（PD-1）轴阻断已被确立为非小细胞肺癌的一种有效治疗方法。程序性死亡配体1（PD-L1）蛋白的免疫组织化学（IHC）检测是唯一可用于指导非小细胞肺癌免疫检查点抑制剂治疗的生物标志物。由于每种PD-1/PD-L1阻断剂都是与临床试验中使用的特定PD-L1 IHC检测方法一起获批的，病理学家面临着在有限样本上进行各种检测的挑战。为了对此有更统一的认识，已经进行了几个平台之间的交叉验证研究，并显示出一致的结果。然而，由于存在将患者错误分类以进行治疗的风险，检测方法的互换性在实际应用中可能受到限制。此外，几个问题，包括肿瘤中PD-L1表达的时空异质性，以及细胞学标本用作PD-L1检测组织样本替代物的可能性，仍未得到解决。未来，免疫治疗研究的主要目标之一应该是找到一种用于PD-1阻断治疗的新型预测生物标志物，以及将其与PD-L1 IHC和其他检测相结合的方法。
