Immune Microenvironment Differences Between Squamous and Non-squamous Non-small-cell Lung Cancer and Their Influence on the Prognosis
Immune Microenvironment Differences Between Squamous and Non-squamous Non-small-cell Lung Cancer and Their Influence on the Prognosis
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鳞状和非鳞状非小细胞肺癌免疫微环境的差异及其对预后的影响
DOI：
10.1016/j.cllc.2018.09.012
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发表时间：
2019-01-01
影响因子：
3.6
通讯作者：
Xing, Ligang
中科院分区：
文献类型：
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作者：
Meng, Xiangjiao;Gao, Yongsheng;Xing, Ligang
本研究旨在阐明鳞状非小细胞肺癌（SQ-NSCLC）和非SQ-NSCLC之间免疫微环境的可能差异。在197例非SQ-NSCLC样本中检测了分化簇8（CD 8+）、分化簇4、转录因子叉头盒P3和程序性死亡配体1的表达。在SQ-NSCLC患者的癌巢中检测到更多的CD 8+肿瘤浸润淋巴细胞。不同的cCD 8+肿瘤浸润淋巴细胞特征表明SQ-NSCLC和non-SQ-NSCLC在免疫微环境方面可能是不同的癌症类型。引言：检查点阻断已进入非小细胞肺癌（NSCLC）的常规临床应用。然而，鳞状（SQ）和非鳞状（非SQ）NSCLC之间抗程序性细胞死亡蛋白1（PD-1）抗体的疗效和缓解预测因子存在一些差异。本研究旨在阐明SQ-NSCLC和non-SQ-NSCLC之间免疫微环境的可能差异及其对预后的影响。患者和方法：共纳入197例I至III期NSCLC患者。采用免疫组织化学方法检测了85例SQ-NSCLC和112例非SQNSCLC样本癌巢和间质中分化簇8（CD 8+）、分化簇4（CD 4+）、转录因子叉头盒P3（FOXP 3+）和程序性死亡配体1（PD-L1）的表达。结果如下：SQ-NSCLC患者的癌巢（cCD 8+）中检测到的CD 8+肿瘤浸润淋巴细胞（TIL）多于非SQ-NSCLC患者（56% vs. 34%; P = .002）。SQ组和非SQ组在其他TIL标志物或PD-L1表达方面无显著差异。多变量分析显示，cCD 8 + TIL浸润程度是SQ-NSCLC组（P = 0.003）和非SQ-NSCLC组（P = 0.024）总生存期（OS）的独立阳性预测因子。在单变量分析中，间质中的CD 8 + TIL、癌巢和间质中的CD 4 + TIL以及癌间质中的FOXP 3 + TIL与非SQ-NSCLC或SQ-NSCLC患者的不同肿瘤相关。使用10%的临界值，PD-L1表达是总NSCLC（P = 0.011）、I期（P = 0.037）、SQ-NSCLC（P = 0.097）和非SQ-NSCLC（P = 0.051）的不良预后因素。结论：不同的cCD 8 + TIL特征和某些TIL的不同预后价值表明，SQ-NSCLC和非SQ-NSCLC在免疫微环境方面可能是不同的癌症类型。(C)2018爱思唯尔公司All rights reserved.
The study aims to elucidate the possible difference in immune microenvironment between squamous non-small-cell lung cancer (SQ-NSCLC) and non-SQ-NSCLC. Cluster of differentiation 8 (CD8+), duster of differentiation 4, transcription factor forkhead box P3, and programmed death-ligand 1 expression were examined on 197 non-SQ-NSCLC samples. More CD8+ tumor infiltrating lymphocytes were detected in the cancer nests from patients with SQ-NSCLC. The different cCD8+ tumor infiltrating lymphocyte profile indicates that SQ-NSCLC and non-SQ-NSCLC are likely different cancer types with respect to their immune microenvironments.Introduction: 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. Patients and Methods: 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-SQNSCLC samples using immunohistochemistry. Results: 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). Conclusion: 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. (C) 2018 Elsevier Inc. All rights reserved.