Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science, Jinan, China.
Department of Pathology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science, Jinan, China.
Clin Lung Cancer. 2019 Jan;20(1):48-58. doi: 10.1016/j.cllc.2018.09.012. Epub 2018 Sep 24.
Checkpoint blockades have entered routine clinical use for non-small-cell lung cancer (NSCLC). However, there were some differences in efficacy and response predictors for anti-programmed cell death protein 1 (PD-1) antibodies between squamous (SQ) and nonsquamous (non-SQ) NSCLC. The study aims to elucidate the possible difference in immune microenvironment between SQ-NSCLC and non-SQ-NSCLC and their influence on the prognosis.
A total of 197 patients with stages I to III NSCLC were included. cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), transcription factor forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) expression were examined in cancer nest and stroma on 85 SQ-NSCLC and 112 non-SQ-NSCLC samples using immunohistochemistry.
More CD8+ tumor infiltrating lymphocytes (TILs) were detected in the cancer nests (cCD8) from patients with SQ-NSCLC than those with non-SQ-NSCLC (56% vs. 34%; P = .002). There were no significant differences between the SQ and non-SQ groups in terms of other TIL markers or PD-L1 expression. Multivariate analysis showed that the degree of cCD8+ TIL infiltration was an independent positive predictor for overall survival (OS) in the SQ-NSCLC group (P = .003) and in the non-SQ-NSCLC group (P = .024). In the univariate analysis, CD8+ TILs in the stroma, CD4+ TILs in the cancer nest and stroma, and FOXP3+ TILs in the cancer stroma associated with different prognoses for patients with either non-SQ-NSCLC or SQ-NSCLC. Using a 10% cutoff, PD-L1 expression was a poor prognostic factor in total NSCLC (P = .011), stage I (P = .037), SQ-NSCLC (P = .097), and non-SQ-NSCLC (P = .051).
The different cCD8+ TIL profile and different prognostic value with certain TILs indicates that SQ-NSCLC and non-SQ-NSCLC are likely different cancer types with respect to their immune microenvironments.
免疫检查点抑制剂已广泛应用于非小细胞肺癌（NSCLC）的临床治疗。然而，抗程序性死亡蛋白 1（PD-1）抗体在鳞状（SQ）和非鳞状（非-SQ）NSCLC 中的疗效和反应预测因素存在差异。本研究旨在阐明 SQ-NSCLC 和非-SQ-NSCLC 之间免疫微环境的可能差异及其对预后的影响。
纳入 197 例 I 至 III 期 NSCLC 患者。采用免疫组织化学法检测 85 例 SQ-NSCLC 和 112 例非-SQ-NSCLC 样本中癌巢和基质中 CD8、CD4、叉头框 P3（FOXP3）和程序性死亡配体 1（PD-L1）的表达。
与非-SQ-NSCLC 患者相比，SQ-NSCLC 患者癌巢中 CD8+肿瘤浸润淋巴细胞（TILs）（cCD8）更多（56% vs. 34%；P=0.002）。SQ 和非-SQ 组之间其他 TIL 标志物或 PD-L1 表达无显著差异。多变量分析显示，cCD8+TIL 浸润程度是 SQ-NSCLC 组（P=0.003）和非-SQ-NSCLC 组（P=0.024）总生存（OS）的独立阳性预测因子。在单变量分析中，基质中的 CD8+TILs、癌巢和基质中的 CD4+TILs 以及癌基质中的 FOXP3+TILs 与非-SQ-NSCLC 或 SQ-NSCLC 患者的不同预后相关。使用 10%的截断值，PD-L1 表达在总 NSCLC（P=0.011）、I 期（P=0.037）、SQ-NSCLC（P=0.097）和非-SQ-NSCLC（P=0.051）中均为不良预后因素。
不同的 cCD8+TIL 特征和某些 TIL 与预后的不同相关性表明，SQ-NSCLC 和非-SQ-NSCLC 可能在免疫微环境方面属于不同的癌症类型。
