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

识别小细胞肺癌中抗 PD-L1/PD-1 免疫疗法、Rova-T 疗法或 EZH2 抑制疗法的候选应答者

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

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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