- Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various cancers and reveal a new era of cancer immunotherapy.
- To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression.
- Representative medical literature regarding PD-L1 expression in various cancers, including the preliminary results of the Blue Proposal, which compares different immunohistochemical stains for PD-L1 reported in the recent American Association of Cancer Research (AACR) Annual Meeting (April 16-20, 2016).
- Either PD-1/PD-L1-targeted therapy alone or in combination with other treatment modalities provides benefit for patients with advanced cancers. Because of the complexity of cancer immunity, we still do not have a reliable biomarker to predict the response of PD-1/PD-L1-targeted therapy. Future studies, including methods beyond immunohistochemical stains, are needed to develop reliable biomarker/biomarkers for pathology laboratories to aid in selecting patients who will benefit most from PD-1/PD-L1-targeted therapy.
背景：包括程序性死亡受体－1/配体－1(PD-1/PD-L1) 通路在内的免疫检查点通路在人体自身免疫耐受、限制自体免疫攻击以及肿瘤细胞的免疫逃逸中起到重要作用。近期的临床试验进一步证明了 PD-1/PD-L1靶向治疗在多种肿瘤中的有效性，就此打开了免疫治疗的新纪元。
结论：PD-1 / PD-L1靶向治疗单用或联合其他治疗方式均为晚期癌症患者带来生存获益。 但由于肿瘤免疫的复杂性，我们仍然没有可靠的生物标志物来预测PD-1 / PD-L1靶向治疗的反应。 需要未来进一步的研究，包括免疫组织化学染色之外的方法，以发现用于病理实验室的可靠生物标志物、以及帮助筛选出将从PD-1 / PD-L1靶向治疗中获益最多患者的生物标志物。