肺鳞状细胞癌中 IDO1 和 PD-L1 的共表达：新型联合治疗的潜在靶点。
Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma: Potential targets of novel combination therapy.
机构信息
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
出版信息
Lung Cancer. 2019 Feb;128:26-32. doi: 10.1016/j.lungcan.2018.12.008. Epub 2018 Dec 10.
OBJECTIVES
Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC).
MATERIALS AND METHODS
The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry.
RESULTS
Among 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P = 0.0011). Kaplan-Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P = 0.0122, P = 0.0303 and P = 0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P = 0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P = 0.0033, P = 0.0003, and P < 0.0001, respectively).
CONCLUSIONS
IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.
目的
联合使用吲哚胺 2,3-双加氧酶 1（IDO1）抑制剂和针对程序性细胞死亡-1（PD-1）/程序性死亡配体 1（PD-L1）的药物有望成为包括非小细胞肺癌（NSCLC）在内的各种实体瘤的一种新的有效治疗选择。因此，阐明 IDO1/PD-L1 共表达肿瘤的临床和病理特征以及 IDO1/PD-L1 共表达与 NSCLC 患者联合治疗疗效之间的关系非常重要。在这项研究中，我们研究了 IDO1/PD-L1 共表达对原发性肺鳞癌（SCC）的预后影响及其与肿瘤浸润淋巴细胞（TIL）的关系。
材料与方法
通过免疫组化法检测 202 例接受手术切除的原发性肺 SCC 患者的 IDO1、PD-L1、Ki-67、分化群 3（CD3）、CD4 和 CD8 的表达水平。
结果
在 202 例患者中，176 例（87.1%）IDO1 表达阳性，106 例（52.5%）PD-L1 表达阳性，99 例（49.0%）同时表达 IDO1/PD-L1 蛋白。Fisher 确切检验显示 IDO1 和 PD-L1 肿瘤比例评分之间存在显著相关性（P=0.0011）。Kaplan-Meier 曲线显示，PD-L1 单独表达以及 IDO1 和 PD-L1 共表达与总生存期较短显著相关，但 IDO1 单独表达则不然（对数秩检验：P=0.0122、P=0.0303 和 P=0.5168）。IDO1 和 PD-L1 共表达患者的 Ki-67 标记指数明显高于无共表达患者（Student's t 检验：P=0.0005）。此外，IDO1/PD-L1 共表达与高 CD3、CD4 和 CD8 表达显著相关（Fisher 确切检验：P=0.0033、P=0.0003 和 P<0.0001）。
结论
IDO1 表达与 PD-L1 表达相关，IDO1 和 PD-L1 共表达可能是肺鳞癌免疫治疗的重要靶点。
Zotero 插件