Tokito Takaaki, Azuma Koichi, Kawahara Akihiko, Ishii Hidenobu, Yamada Kazuhiko, Matsuo Norikazu, Kinoshita Takashi, Mizukami Naohisa, Ono Hirofumi, Kage Masayoshi, Hoshino Tomoaki
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Eur J Cancer. 2016 Mar;55:7-14. doi: 10.1016/j.ejca.2015.11.020. Epub 2016 Jan 6.
BACKGROUND: Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis. RESULTS: Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups. CONCLUSIONS: Among stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC.
背景:已知程序性细胞死亡配体1(PD-L1)的表达是癌症逃避免疫监视的一种机制,但对于局部晚期非小细胞肺癌(NSCLC)患者疗效的预测因素知之甚少。我们研究了接受同步放化疗(CCRT)的局部晚期NSCLC患者中PD-L1表达和CD8 +肿瘤浸润淋巴细胞(TILs)密度的预测相关性。 方法:我们回顾性分析了74例连续接受CCRT的III期NSCLC患者。通过免疫组织化学分析评估PD-L1表达和CD8 + TIL密度。 结果:单因素和多因素分析表明,CD8 + TIL密度是无进展生存期(PFS)和总生存期(OS)的独立且显著的预测因素,而PD-L1表达与PFS和OS无关。亚组分析显示,通过四个亚组的Kaplan-Meier曲线,PD-L1 + / CD8低组的PFS最短(8.6个月,p = 0.02)和OS(13.9个月,p = 0.11),而PD-L1 - / CD8高组的预后最长(中位PFS和OS未达到)。 结论:在接受CCRT的III期NSCLC患者中,表达PD-L1的患者有生存较差的趋势。我们的分析表明,PD-L1表达缺失与CD8 + TIL密度相结合与这些患者的良好生存显著相关。建议将PD-L1表达与CD8 + TIL密度相结合可作为III期NSCLC患者有用的预测生物标志物。
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