Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
Oncol Rep. 2020 Aug;44(2):424-437. doi: 10.3892/or.2020.7643. Epub 2020 Jun 11.
Checkpoint inhibitor‑based immunotherapy has exhibited unprecedented success in the treatment of advanced‑stage cancer in recent years. Several therapeutic antibodies targeting programmed death‑1 (PD‑1) or its ligand (PD‑L1) have received regulatory approvals for the treatment of multiple malignancies, including melanoma, non‑small cell lung cancer, kidney cancer and Hodgkin's lymphoma. However, a substantial proportion of patients still do not benefit from these agents, let alone the risk of immune‑associated toxicities and financial burden. Therefore, it is imperative to identify valid predictive biomarkers which can help optimize the selection of patients. In this review, a mechanism‑based interpretation of tumor PD‑L1 expression and other candidate biomarkers of response to antitumor PD‑1/PD‑L1 blockade was provided, particularly for the tumor microenvironment‑derived 'immunomes', and the challenges faced in their clinical use was addressed. Directions for future biomarker development and the potential of combined biomarker strategies were also proposed.
近年来，基于检查点抑制剂的免疫疗法在晚期癌症治疗方面取得了前所未有的成功。几种针对程序性死亡受体 1（PD-1）或其配体（PD-L1）的治疗性抗体已获得监管部门批准，可用于治疗多种恶性肿瘤，包括黑色素瘤、非小细胞肺癌、肾癌和霍奇金淋巴瘤。然而，相当一部分患者仍然不能从这些药物中获益，更不用说免疫相关毒性和经济负担的风险了。因此，确定有效的预测生物标志物来帮助优化患者选择是当务之急。在这篇综述中，我们基于机制解释了肿瘤 PD-L1 表达和其他抗肿瘤 PD-1/PD-L1 阻断反应的候选生物标志物，特别是肿瘤微环境衍生的“免疫组”，并讨论了它们在临床应用中面临的挑战。还提出了未来生物标志物开发的方向和联合生物标志物策略的潜力。
