Department of Pulmonology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
Department of Immunology, University Hospital Zurich, Gloriastrasse 23, 8091, Zurich, Switzerland.
Cancer Immunol Immunother. 2021 Jul;70(7):1867-1876. doi: 10.1007/s00262-020-02798-z. Epub 2021 Jan 4.
Lung cancer is the leading cause of death by cancer. In recent years, immunotherapy with checkpoint inhibitors (ICI) emerged as a promising new therapeutic approach. However, a deeper understanding of the immunologic responses adjacent to the tumor known as tumor microenvironment (TME) is needed. Our study investigated TME of lung cancer by analyzing cytokines in bronchoalveolar lavage fluid (BALF).
Between January 2018 and June 2019, 119 patients were prospectively enrolled in this study. For each cancer patient, levels of 16 cytokines (fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukins (IL): IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, and IL-23) were measured in BALF and serum and compared to healthy individuals and patients with other lung diseases.
There were several significant differences of cytokine levels of patients with lung cancer compared to healthy individuals. However, none of them remained in the multivariate analysis compared to other lung diseases in either BALF or serum. Furthermore, there were no significant differences between the groups in cell differentiation of either BALF or serum. Cytokine levels in BALF were generally near the lower detection limit and showed almost no correlation with their respective levels measured in serum of the same individual.
Cytokines in BALF and serum of lung cancer patients may indicate unspecific inflammation. BAL is not recommendable as a tool to investigate TME of lung cancer. Therefore, cytokines measured in BALF are probably not appropriate as predictors in patients treated with ICIs.
肺癌是癌症死亡的主要原因。近年来，免疫检查点抑制剂（ICI）的免疫疗法作为一种有前途的新治疗方法出现。然而，需要更深入地了解肿瘤旁的免疫反应，即肿瘤微环境（TME）。我们通过分析支气管肺泡灌洗液（BALF）中的细胞因子来研究肺癌的 TME。
2018 年 1 月至 2019 年 6 月，我们前瞻性地纳入了 119 名患者进行这项研究。对于每个癌症患者，均测量 BALF 和血清中 16 种细胞因子（趋化因子 fractalkine、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）和白细胞介素（IL）：IL-1b、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12p70、IL-13、IL-17A 和 IL-23）的水平，并与健康个体和患有其他肺部疾病的患者进行比较。
与健康个体相比，肺癌患者的细胞因子水平存在一些显著差异。然而，在 BALF 或血清中与其他肺部疾病进行多变量分析时，没有一种细胞因子水平具有统计学意义。此外，BALF 和血清中细胞分化在各组之间也没有显著差异。BALF 中的细胞因子水平通常接近检测下限，并且与同一个体血清中测量的相应水平几乎没有相关性。
肺癌患者的 BALF 和血清中的细胞因子可能表明存在非特异性炎症。BAL 不推荐作为研究肺癌 TME 的工具。因此，ICI 治疗患者中测量的 BALF 细胞因子可能不适合作为预测指标。
