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

• Published in: Journal of cancer research and clinical oncology Vol. 146; no. 10; pp. 2639 - 2650
• Main Authors: Takada, Kazuki, Toyokawa, Gouji, Kinoshita, Fumihiko, Jogo, Tomoko, Kohashi, Kenichi, Wakasu, Sho, Ono, Yuki, Tanaka, Kensuke, Oba, Taro, Osoegawa, Atsushi, Tagawa, Tetsuzo, Azuma, Koichi, Okamoto, Isamu, Shimokawa, Mototsugu, Oda, Yoshinao, Mori, Masaki
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2020; Springer Nature B.V
• Subjects: Adenocarcinoma; Apoptosis; Cancer Research; CD8 antigen; Cell death; Cell differentiation; Hematology; Immunotherapy; Internal Medicine; Ligands; Lung cancer; Lymphocytes; Medicine; Medicine & Public Health; Oncology; Original Article – Clinical Oncology; PD-L1 protein; Tryptophan 2,3-dioxygenase; Tumor cells; Tumor-infiltrating lymphocytes; PD-L1; PD-L2; Lung adenocarcinoma; CD8; IDO1
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-020-03250-6

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 tumor-infiltrating 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.