嗜酸性粒细胞扭曲了中性粒细胞的成熟并使Th17细胞极化,从而促进了肺腺癌的发展

IF 5.9 2区 医学 Q1 ONCOLOGY Oncogenesis Pub Date : 2024-04-03 DOI:10.1038/s41389-024-00513-6
Joshua K. Stone, Natalia von Muhlinen, Chenran Zhang, Ana I. Robles, Amy L. Flis, Eleazar Vega-Valle, Akihiko Miyanaga, Masaru Matsumoto, K. Leigh Greathouse, Tomer Cooks, Giorgio Trinchieri, Curtis C. Harris
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引用次数: 0

摘要

瘤内微生物组的变化是肺癌和其他癌症的共同特征,可能会影响肿瘤微环境中的炎症和免疫,从而影响生长和转移。我们以前曾对患者的肺癌微生物组进行过鉴定,发现Acidovorax temperans富集在肿瘤中。在这里,我们在一个由突变 K-ras 和 Tp53 驱动的动物模型中灌输了节肢动物。这表明A. temperans通过促炎细胞的浸润加速了肿瘤的发展和负担。暴露于A. temperans的中性粒细胞表现出成熟的促肿瘤表型,细胞因子信号转导增加,IL-1β信号转导发生全面转移。中性粒细胞到单核细胞和巨噬细胞的信号传导上调了 MHC II,从而激活了 CD4+ T 细胞,使其极化为可在 CD4+ 和 γδ 群体(T17)中检测到的 IL-17A+ 表型。这些T17细胞具有共同的基因表达程序,可预测人类LUAD的不良存活率。这些数据表明,细菌暴露会通过调节炎症促进肿瘤生长。
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Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development

Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified Acidovorax temperans as enriched in tumors. Here, we instilled A. temperans in an animal model driven by mutant K-ras and Tp53. This revealed A. temperans accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+ T cells, polarizing them to an IL-17A+ phenotype detectable in CD4+ and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.

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来源期刊
Oncogenesis
Oncogenesis ONCOLOGY-
CiteScore
11.90
自引率
0.00%
发文量
70
审稿时长
26 weeks
期刊介绍: Oncogenesis is a peer-reviewed open access online journal that publishes full-length papers, reviews, and short communications exploring the molecular basis of cancer and related phenomena. It seeks to promote diverse and integrated areas of molecular biology, cell biology, oncology, and genetics.
期刊最新文献
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