Cottrell Tricia R, Taube Janis M
Cancer J. 2018 Jan/Feb;24(1):41-46. doi: 10.1097/PPO.0000000000000301.
PD-L1 checkpoint blockade is revolutionizing cancer therapy, and biomarkers capable of predicting which patients are most likely to respond are highly desired. The detection of PD-L1 protein expression by immunohistochemistry can enrich for response to anti-PD-(L)1 blockade in a variety of tumor types, but is not absolute. Limitations of current commercial PD-L1 immunohistochemical (IHC) assays and improvements anticipated in next-generation PD-L1 testing are reviewed. Assessment of tumor-infiltrating lymphocytes in conjunction with PD-L1 testing could improve specificity by distinguishing adaptive (interferon γ driven and cytotoxic T-lymphocyte associated) from constitutive (non-immune mediated) expression. The presence of a high tumor mutational burden also enriches for response to therapy, and early data indicate that this may provide additive predictive value beyond PD-L1 IHC alone. As candidate biomarkers continue to emerge, the pathologist's assessment of the tumor microenvironment on hematoxylin-eosin stain combined with PD-L1 IHC remains a rapid and robust way to evaluate the tumor-immune dynamic.
程序性死亡受体 1 配体（PD-L1）检查点阻断正在彻底改变癌症治疗方式，因此人们迫切需要能够预测哪些患者最可能产生反应的生物标志物。通过免疫组织化学检测 PD-L1 蛋白表达，可使多种肿瘤类型对抗 PD-（L）1 阻断产生反应，但并非绝对如此。本文综述了当前商用 PD-L1 免疫组织化学（IHC）检测方法的局限性以及下一代 PD-L1 检测有望实现的改进。结合 PD-L1 检测评估肿瘤浸润淋巴细胞，通过区分适应性（由干扰素γ驱动且与细胞毒性 T 淋巴细胞相关）和组成性（非免疫介导）表达，可提高检测的特异性。肿瘤突变负荷高也预示着对治疗有反应，早期数据表明，这可能比单独的 PD-L1 IHC 检测具有额外的预测价值。随着候选生物标志物不断涌现，病理学家通过苏木精 - 伊红染色结合 PD-L1 IHC 对肿瘤微环境进行评估，仍然是评估肿瘤免疫动态的一种快速且可靠的方法。
