Expression of PD-L1, PD-L2, and IDO1 on tumor cells and density of CD8-positive tumor-infiltrating lymphocytes in early-

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ORIGINAL ARTICLE – CLINICAL ONCOLOGY

Expression of PD‑L1, PD‑L2, and IDO1 on tumor cells and density of CD8‑positive tumor‑infiltrating lymphocytes in early‑stage lung adenocarcinoma according to histological subtype Kazuki Takada1   · Gouji Toyokawa2 · Fumihiko Kinoshita1 · Tomoko Jogo1,3 · Kenichi Kohashi3 · Sho Wakasu1 · Yuki Ono1 · Kensuke Tanaka1 · Taro Oba1 · Atsushi Osoegawa1 · Tetsuzo Tagawa1 · Koichi Azuma4 · Isamu Okamoto5 · Mototsugu Shimokawa6 · Yoshinao Oda3 · Masaki Mori1 Received: 26 November 2019 / Accepted: 6 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Purpose  This study examined the expression of programmed cell death-ligand 1 (PD-L1), programmed cell death-ligand 2 (PD-L2), and indoleamine 2,3-dioxygenase-1 (IDO1) in tumor cells and cluster of differentiation 8 (CD8)-positive tumorinfiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma according to histological subtypes. Methods  We evaluated PD-L1, PD-L2, and IDO1 expression in tumor cells and CD8-positive TILs in surgically resected specimens from 196 stage 0 or I lung adenocarcinoma patients by immunohistochemical staining. We also examined the relationships between the expression of PD-L1, PD-L2, and IDO1 in tumor cells and the density of CD8-positive TILs and clinical factors. Patients were divided into three groups: A, adenocarcinoma in situ and minimally invasive adenocarcinoma (N = 32); B, lepidic predominant invasive adenocarcinoma (IAD; LPA; N = 66); and C, IAD except for LPA (N = 98). Results  PD-L1 was expressed only in Group C, but not in Groups A or B. The positive ratio of PD-L2 was significantly higher in Group C (63.3%), and that of IDO1 was also significantly higher in Group C (65.3%). The density of CD8-positive TILs was significantly higher in Group C (45 ± 2.4). There was no significant difference between the positive ratios of PD-L2 and IDO1 and the density of CD8-positive TILs in Group A (50.0%, 21.9%, and 36 ± 4.1, respectively) or Group B (60.6%, 25.8%, and 44 ± 3.0, respectively). Conclusions  No cases in Groups A and B expressed PD-L1. The expression of immune-related factors, especially PD-L1 and IDO1, was significantly associated with Group C. This is the first report of the detailed examination of PD-L1, PD-L2, IDO1, and CD8 expression in lung adenocarcinoma subtypes with lepidic predominant components. Our results could help identify patients who would benefit from perioperative immunotherapy. Keywords  PD-L1 · PD-L2 · IDO1 · CD8 · Lung adenocarcinoma

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Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3‑1‑1 Maidashi, Higashi‑ku, Fukuoka 812‑8582, Japan

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume‑shi, Fukuoka 830‑0011, Japan

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Department of Thoracic Surgery, National Hospital Organization Kyushu Medical Center, 1‑8‑1 Jigyohama, Chuo‑ku, Fukuoka 810‑8563, Japan

Research Institute for Diseases of the Chest, Graduate