Saito Motonobu, Saito Katsuharu, Shiraishi Kouya, Maeda Daichi, Suzuki Hiroyuki, Minamiya Yoshihiro, Kono Koji, Kohno Takashi, Goto Akiteru
Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1295, Japan.
Mol Clin Oncol. 2018 Feb;8(2):310-314. doi: 10.3892/mco.2017.1536. Epub 2017 Dec 12.
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared. It was demonstrated that 1/20 patients (5.0%) exhibited positive PD-L1 expression in the metastatic lesions, as well as in the primary lung tumor. DLL3 was highly expressed in 14/20 patients (70%) and EZH2 was positive in 17/20 patients (85%). None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy.
一种用于小细胞肺癌（SCLC）治疗的有效候选方法是针对程序性死亡1（PD-1）及其配体PD-L1的免疫检查点阻断疗法。此外，靶向δ样蛋白3（DLL3）的抗体药物偶联物罗伐匹妥珠单抗（Rova-T）和zeste同源物2（EZH2）抑制剂有望成为SCLC的首个靶向治疗方法。本研究的目的是评估SCLC中PD-L1、DLL3和EZH2的表达，以寻找对这些疗法有反应的候选者。对20例SCLC患者进行了PD-L1、DLL3和EZH2的免疫组织化学（IHC）染色，并比较了临床病理特征和IHC染色强度。结果表明，20例患者中有1例（5.0%）在转移灶以及原发性肺肿瘤中均表现出PD-L1阳性表达。14/20例患者（70%）DLL3高表达，17/20例患者（85%）EZH2阳性。这些病例均与年龄、性别、吸烟、分期或治疗无任何相关性，而IHC染色能够识别抗PD-L1/PD-1免疫疗法、Rova-T疗法或EZH2抑制剂疗法的候选反应者。
