Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Thoracic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka, 810-8563, Japan.
J Cancer Res Clin Oncol. 2020 Oct;146(10):2639-2650. doi: 10.1007/s00432-020-03250-6. Epub 2020 May 14.
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.
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).
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).
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.
本研究根据组织学亚型，检测早期肺腺癌中肿瘤细胞程序性死亡配体 1（PD-L1）、程序性死亡配体 2（PD-L2）和吲哚胺 2,3-双加氧酶-1（IDO1）在肿瘤细胞和 CD8 阳性肿瘤浸润淋巴细胞（TIL）中的表达。
通过免疫组织化学染色，评估了 196 例 0 期或 I 期肺腺癌手术切除标本中肿瘤细胞 PD-L1、PD-L2 和 IDO1 的表达，并分析了 PD-L1、PD-L2 和 IDO1 在肿瘤细胞中的表达与 CD8 阳性 TIL 密度和临床因素之间的关系。患者分为三组：A 组，原位腺癌和微浸润性腺癌（n=32）；B 组，以贴壁生长为主的浸润性腺癌（LPA；n=66）；C 组，除 LPA 以外的以贴壁生长为主的浸润性腺癌（n=98）。
PD-L1 仅在 C 组表达，而在 A 组和 B 组不表达。C 组 PD-L2 阳性率显著较高（63.3%），IDO1 阳性率也显著较高（65.3%）。C 组 CD8 阳性 TIL 密度显著较高（45±2.4）。A 组（50.0%、21.9%和 36±4.1）或 B 组（60.6%、25.8%和 44±3.0）中 PD-L2 和 IDO1 的阳性率与 CD8 阳性 TIL 密度之间无显著差异。
A 组和 B 组均无 PD-L1 表达。免疫相关因子的表达，尤其是 PD-L1 和 IDO1，与 C 组显著相关。这是首次对以贴壁生长为主的肺腺癌亚型中 PD-L1、PD-L2、IDO1 和 CD8 表达进行详细检查的报告。我们的研究结果可能有助于确定受益于围手术期免疫治疗的患者。
