Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Cancer Med. 2018 Jan;7(1):32-45. doi: 10.1002/cam4.1243. Epub 2017 Nov 23.
To investigate the prognostic value of PD-L1 expression combined with CD8 TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8 TILs, and oncogenic alterations. PD-L1 was detected in 71 (39.9%) and CD8 TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR were associated with both PD-L1 and CD8 TILs. Patients with CD8 TILs had longer OS (P = 0.012). PD-L1 was significantly associated with longer OS in patients with oncogenic alterations (P = 0.047). By multivariate analysis, CD8 TILs (HR = 0.411; 95% CI, 0.177-0.954; P = 0.038), rather than PD-L1, was the independent predictive factor for OS. The longest and shortest OS were achieved in patients with PD-L1 /CD8 and PD-L1 /CD8 , respectively (P = 0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%) patients with primary and matched metastatic lymph node specimens. Of them, CD8 TILs was significantly associated with longer OS in patients with metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049, respectively). The combination of PD-L1 and CD8 TILs density, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC needs to be evaluated more comprehensively.
为了探究 PD-L1 表达与 CD8 TIL 密度联合在可切除 NSCLC 患者中的预后价值，并分析其与临床病理特征的相关性。我们回顾性纳入了 2011 年至 2015 年间 178 例接受手术治疗的 NSCLC 患者。所有手术原发肿瘤和 58 例匹配的转移淋巴结标本均进行 PD-L1、CD8 TIL 和致癌改变的检测。71 例（39.9%）和 74 例（41.6%）患者的 PD-L1 和 CD8 TIL 表达呈阳性。吸烟、鳞状细胞癌和 EGFR 与 PD-L1 和 CD8 TIL 均相关。CD8 TIL 阳性的患者总生存期（OS）更长（P=0.012）。PD-L1 与存在致癌改变的患者 OS 更长显著相关（P=0.047）。多因素分析显示，CD8 TIL（HR=0.411；95%CI，0.177-0.954；P=0.038）而非 PD-L1 是 OS 的独立预测因素。PD-L1/CD8 和 PD-L1/CD8 患者的 OS 最长和最短（P=0.025）。在 58 例患者中，23 例（39.7%）的原发肿瘤和匹配的转移淋巴结标本中 PD-L1 表达不一致。其中，在存在转移淋巴结和/或 PD-L1 表达一致的患者中，CD8 TIL 与 OS 更长显著相关（P=0.017 和 0.049）。PD-L1 和 CD8 TIL 密度的联合而非 PD-L1 表达水平，提示 NSCLC 患者具有显著的预后价值。在接受手术治疗的 NSCLC 患者中，仅有不到一半的患者在原发和转移病灶中存在 PD-L1 表达不一致的情况。晚期 NSCLC 患者的 PD-L1 表达水平需要更全面的评估。
