Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Clinical Pathology, Kobe City Medical Center General Hospital, Kobe, Japan.
Sci Rep. 2017 Sep 12;7(1):11373. doi: 10.1038/s41598-017-11949-9.
Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. A total of 45 patients with LA-NSCLC were included, among which there were sufficient pre- and post-CCRT specimens in 35 patients. Overall, the percentage of tumor cells with PD-L1 expression significantly decreased between pre- and post-CCRT specimens (P = 0.024). Sixteen, 15, and 4 patients had decreased, unchanged, or increased PD-L1 expression after CCRT, respectively. Median OS of patients with decreased, unchanged, or increased PD-L1 expression was 85.1, 92.8, and 14.6 months, respectively (P < 0.001). In conclusion, the percentage of PD-L1-positive tumor cells significantly decreased after CCRT. Alteration of PD-L1 expression after neoadjuvant CCRT was associated with prognosis in patients with LA-NSCLC. These data should be considered when developing the optimal approach of integrating PD-1 axis inhibitors with CCRT.
同期放化疗（CCRT）是局部晚期非小细胞肺癌（LA-NSCLC）的治疗选择。几项临床试验正在开发中将程序性细胞死亡 1（PD-1）轴抑制剂与放射疗法结合用于 LA-NSCLC 患者。然而，CCRT 对肿瘤细胞程序性死亡配体-1（PD-L1）表达的影响尚不清楚。在这项研究中，我们分析了预先和 CCRT 后获得的配对 NSCLC 标本。通过免疫组织化学研究肿瘤细胞上的 PD-L1 表达。共纳入 45 例 LA-NSCLC 患者，其中 35 例有足够的预先和 CCRT 后标本。总体而言，肿瘤细胞上 PD-L1 表达的百分比在预先和 CCRT 后标本之间显著降低（P = 0.024）。16、15 和 4 例患者分别在 CCRT 后 PD-L1 表达减少、不变或增加。PD-L1 表达减少、不变或增加的患者的中位 OS 分别为 85.1、92.8 和 14.6 个月（P < 0.001）。总之，CCRT 后 PD-L1 阳性肿瘤细胞的百分比显著降低。LA-NSCLC 患者新辅助 CCRT 后 PD-L1 表达的改变与预后相关。在开发将 PD-1 轴抑制剂与 CCRT 相结合的最佳方法时，应考虑这些数据。
