1 Division of Pulmonary and Critical Care, and.
2 Clinical Research Division and.
Am J Respir Crit Care Med. 2018 Feb 1;197(3):325-336. doi: 10.1164/rccm.201704-0795OC.
Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality, and the pathogenesis of both involves aberrant immune functioning.
To profile immune cell composition and function in patients with NSCLC and describe the effects of COPD on lung and tumor microenvironments.
We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC. A murine cigarette smoke exposure model was used to evaluate the effect on pulmonary immune populations. A separate retrospective cohort of patients who received immune checkpoint inhibitors (ICIs) was analyzed, and their survival was quantified.
We observed an increased number of IFN-γ-producing CD8 and CD4 (T-helper cell type 1 [Th1]) lymphocytes in the lungs of patients with COPD. In both humans and mice, increased Th17 content was seen with smoke exposure, but was not associated with the development or severity of COPD. COPD-affected lung tissue displayed increased Th1 differentiation that was recapitulated in the matching tumor sample. PD-1 (programmed cell death protein 1) expression was increased in tumors of patients with COPD, and the presence of COPD was associated with progression-free survival in patients treated with ICIs.
In patients with COPD, Th1 cell populations were expanded in both lung and tumor microenvironments, and the presence of COPD was associated with longer progression-free intervals in patients treated with ICIs. This has implications for understanding the immune mediators of COPD and developing novel therapies for NSCLC.
慢性阻塞性肺疾病（COPD）和非小细胞肺癌（NSCLC）是相互关联的疾病，死亡率很高，两者的发病机制都涉及异常的免疫功能。
分析 NSCLC 患者的免疫细胞组成和功能，并描述 COPD 对肺部和肿瘤微环境的影响。
我们通过对来自 NSCLC 切除术前瞻性队列中患有和不患有 COPD 的患者的切除肺和肿瘤组织进行流式细胞术和 T 细胞受体测序，来对其进行分析。使用香烟烟雾暴露模型来评估对肺部免疫群体的影响。还分析了另一个接受免疫检查点抑制剂（ICI）治疗的患者的回顾性队列，并对其生存率进行了量化。
我们观察到 COPD 患者肺部产生 IFN-γ 的 CD8 和 CD4（辅助性 T 细胞 1 [Th1]）淋巴细胞数量增加。在人类和小鼠中，随着烟雾暴露，Th17 含量增加，但与 COPD 的发展或严重程度无关。受 COPD 影响的肺组织显示出 Th1 分化增加，在匹配的肿瘤样本中也观察到这种情况。PD-1（程序性细胞死亡蛋白 1）在 COPD 患者的肿瘤中表达增加，并且 COPD 的存在与接受 ICI 治疗的患者无进展生存期相关。
在 COPD 患者中，Th1 细胞群在肺部和肿瘤微环境中均扩增，并且 COPD 的存在与接受 ICI 治疗的患者无进展间隔延长相关。这对理解 COPD 的免疫调节剂以及为 NSCLC 开发新的治疗方法具有重要意义。
