Duruisseaux Michaël, Rouquette Isabelle, Adam Julien, Cortot Alexis, Cazes Aurélie, Gibault Laure, Damotte Diane, Lantuejoul Sylvie
Unité d'oncologie thoracique, clinique de pneumologie, centre hospitalier universitaire Grenoble-Alpes, 38043 Grenoble, France.
Service d'anatomie et cytologie pathologiques, pôle IUC oncopole CHU, institut universitaire du cancer de Toulouse-oncopole, 31100 Toulouse, France.
Ann Pathol. 2017 Feb;37(1):61-78. doi: 10.1016/j.annpat.2016.12.009. Epub 2017 Feb 3.
Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1 environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1 inhibitors. In advanced NSCLC, PD1/PD-L1 inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1. PD1/PD-L1 inhibitors are currently tested in mesothelioma and thymic tumors. PD-L1 expression evaluated with immunochemistry is the most studied predictive biomarker of PD1/PD-L1 inhibitor efficacy. Tumor and immune cell expression of PD-L1 is still difficult to evaluate because of intra-tumoral heterogeneity and expression modulation by the microenvironment. Four commercial diagnostic antibodies are in development, with differences concerning recognized epitopes, methodology of evaluation of PD-L1 expression, positivity threshold, kit and platforms used. Clinical trials in NSCLC have shown that patients with tumors strongly positive for PD-L1 derived the best clinical benefit with PD1/PD-L1 inhibitors whereas clinical benefit is less common in tumors negative for PD-L1. PD-L1 expression is not a perfect biomarker since some PD-L1 negative NSCLC respond to PD1/PD-L1 inhibitors and some PD-L1 positive NSCLC do not. PD-L1 testing is likely to be implemented in daily practice for selection of advanced NSCLC that will be treated with pembrolizumab, underscoring the relevance of ongoing harmonization studies of the use of the different antibodies available for PD-L1 testing.
肿瘤免疫环境是癌症的主要组成部分。其组成和组织结构代表了肿瘤的可重复特征以及经过验证的预后因素。在非小细胞肺癌（NSCLC）中，与Th1环境和三级淋巴结构相关的细胞毒性T CD8 +淋巴细胞密度会影响生存率。肿瘤细胞与免疫细胞的相互作用是PD1 / PD-L1抑制剂的作用靶点。在晚期NSCLC中，PD1 / PD-L1抑制剂比二线化疗更有效。帕博利珠单抗在PD-L1强阳性的NSCLC中优于一线化疗。目前正在间皮瘤和胸腺肿瘤中测试PD1 / PD-L1抑制剂。用免疫化学评估的PD-L1表达是研究最多的PD1 / PD-L1抑制剂疗效预测生物标志物。由于肿瘤内异质性和微环境对表达的调节作用，PD-L1在肿瘤和免疫细胞中的表达仍然难以评估。四种商业诊断抗体正在研发中，它们在识别表位、PD-LI表达评估方法、阳性阈值、所用试剂盒和平台方面存在差异。NSCLC的临床试验表明，PD-L1强阳性肿瘤患者使用PD1 / PD-L1抑制剂可获得最佳临床获益，而PD-L1阴性肿瘤患者的临床获益则较少见。PD-L1表达不是一个完美的生物标志物，因为一些PD-L1阴性的NSCLC对PD1 / PD-L1抑制剂有反应，而一些PD-L1阳性的NSCLC则没有反应。PD-L1检测可能会在日常实践中用于选择将接受帕博利珠单抗治疗的晚期NSCLC，这突出了正在进行的关于用于PD-L1检测的不同抗体使用的协调研究的相关性。
