Identification of candidate responders for anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitory therapy in small-cell lung cancer

Saito,Motonobu; Saito,Katsuharu; Shiraishi,Kouya; Maeda,Daichi; Suzuki,Hiroyuki; Minamiya,Yoshihiro; Kono,Koji; Kohno,Takashi; Goto,Akiteru

doi:10.3892/mco.2017.1536

Identification of candidate responders for anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitory therapy in small-cell lung cancer

Authors:
- Motonobu Saito
- Katsuharu Saito
- Kouya Shiraishi
- Daichi Maeda
- Hiroyuki Suzuki
- Yoshihiro Minamiya
- Koji Kono
- Takashi Kohno
- Akiteru Goto
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Affiliations: 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, Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Akita 010‑8543, Japan, Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960‑1295, Japan, Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita, Akita 010‑8543, Japan
Published online on: December 12, 2017 https://doi.org/10.3892/mco.2017.1536
Pages: 310-314

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Abstract

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.

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