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外周炎症伴嗜酸性粒细胞或中性粒细胞增多与 NSCLC 不同组织学亚组患者肿瘤内嗜酸性粒细胞的生存和浸润有关。

Peripheral Inflammation Featuring Eosinophilia or Neutrophilia Is Associated with the Survival and Infiltration of Eosinophils within the Tumor among Various Histological Subgroups of Patients with NSCLC.

机构信息

Institute of Laboratory Medicine, German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Medical Faculty, Philipps University of Marburg, 35043 Marburg, Germany.

Institute of Tumor Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35043 Marburg, Germany.

出版信息

Int J Mol Sci. 2024 Sep 3;25(17):9552. doi: 10.3390/ijms25179552.

Abstract

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment.

摘要

免疫激活状态决定非小细胞肺癌(NSCLC)的预后,已有报道称 T 辅助型 2(TH2)反应呈阳性/阴性相关,包括过敏原特异性 IgE 和嗜酸性粒细胞。我们的研究旨在探讨这些合并免疫反应对 NSCLC 患者生存率的潜在影响。我们的回顾性研究使用了德国肺研究中心(DZL)数据仓库和海德堡胸科医院肺部生物库的数据。我们在一个包含 3143 例 NSCLC 患者的炎症队列中,估计了血液嗜酸性粒细胞和嗜中性粒细胞增多与生存率的关联。我们还在一个包含 212 例 NSCLC 患者的合并症队列中检测了对食物和吸入物的致敏以及高敏 C 反应蛋白(hs-CRP)。最后,我们在一个包含 60 例 NSCLC 患者的组织炎症亚组中,估计了包括嗜酸性粒细胞、T 细胞和肥大细胞在内的免疫相关细胞的浸润。对至少一种食物或吸入物的致敏(sIgE)在腺癌(adeno-LC)患者中高于非腺癌(non-adeno-LC)患者。此外,非腺癌(non-adeno-LC)患者的 hs-CRP 高于腺癌(adeno-LC)患者。外周炎症,特别是嗜酸性粒细胞增多和嗜中性粒细胞增多,与 NSCLC 的不良生存结果相关,在组织学亚组之间存在明显差异。最后,血液嗜酸性粒细胞增多与肺部肿瘤周围组织中显著的嗜酸性粒细胞浸润平行。这项研究提供了外周炎症(嗜酸性粒细胞增多和嗜中性粒细胞增多)与总生存之间的重要作用的新视角,突出了 NSCLC 亚组(adeno-LC 与 non-adeno-LC)之间的区别。外周嗜酸性粒细胞增多增强了肿瘤内的嗜酸性粒细胞浸润。这揭示了炎症、嗜酸性粒细胞浸润与各种组织学亚型 NSCLC 预后之间的复杂相互作用。需要进一步的研究来强调不同组织学亚组中嗜酸性粒细胞在 NSCLC 中的作用及其在塑造肿瘤微环境中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88b/11395097/e1820158d344/ijms-25-09552-g001.jpg

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