DataSheet_4_Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity.xlsx

BackgroundLung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.MethodsWe analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.ResultsIL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.ConclusionThe IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.

背景肺腺癌的磨玻璃样不透明（GGOs）是其早期表现形式。研究GGO的免疫微环境变化，对于阐明早期肺腺癌的发生和演变具有重要意义。尽管IL-6和NK细胞在肺腺癌中的变化已引起全球关注，但我们对其在肺GGO中如何影响早期肺腺癌的进展仍缺乏深入了解。方法：我们分析了21例具有GGO特征的肺腺癌患者的手术标本RNA测序数据，并在TCGA和GEO数据库中验证了IL-6和其他重要免疫分子表达的变化。随后，我们利用流式细胞术检测了GGO和正常肺组织中重要Th1/Th2细胞因子的蛋白表达水平以及肿瘤浸润淋巴细胞（TILs）组成比的变化。接着，我们通过类器官培养和免疫荧光分析IL-6对NK细胞的影响。最后，我们探讨了相关分子和通路的变化。结果：IL-6可能在早期肺腺癌的肿瘤微环境中发挥重要作用。进一步研究证实，GGO组织中IL-6的减少与NK细胞的变化一致，似乎这两种现象之间存在相关性。结论：早期肺腺癌作为GGO的IL-6表达状态和NK细胞水平显著降低，IL-6的刺激可以上调或激活GGO中的NK细胞，为早期肺癌的诊断和发病机制提供了新的见解。