IFNγ和TNFα驱动人类非小细胞肺癌癌症相关成纤维细胞的炎症分泌谱。

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2025-01-01 DOI:10.1002/1873-3468.15083

Lilian Koppensteiner, Layla Mathieson, Liam Neilson, Richard A O'Connor, Ahsan R Akram

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引用次数: 0

摘要

癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）的主要非恶性成分。尽管CAF亚群的驱动因素尚不完全清楚，但在实体肿瘤中，CAF表现出高度的肿瘤间和肿瘤内异质性。在这里，我们证明非小细胞肺癌（NSCLC）患者源性CAFs通过IFNγ和TNFα与抗cd3 /抗cd28刺激的外周血单核细胞（PBMCs）体外共培养，上调炎症因子（IL6、LIF、IL33、GM-CSF、IL1ra）和趋化因子（CCL2、CCL3、CCL4、CCL20、CXCL8、CXCL9、CXCL10、CXCL11）的分泌。此外，t细胞来源的IFNγ在体外抑制CAFs分泌CXCL12。我们的研究结果强调了t细胞效应细胞因子调节非小细胞肺癌CAF分泌组的能力。

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IFNγ and TNFα drive an inflammatory secretion profile in cancer-associated fibroblasts from human non-small cell lung cancer.

Cancer-associated fibroblasts (CAFs) are the dominant nonmalignant component of the tumour microenvironment (TME). CAFs demonstrate a high level of inter- and intra-tumour heterogeneity in solid tumours, though the drivers of CAF subpopulations are not fully understood. Here, we demonstrate that non-small cell lung cancer (NSCLC) patient-derived CAFs upregulate the secretion of inflammatory cytokines (IL6, LIF, IL33, GM-CSF, IL1ra) and chemokines (CCL2, CCL3, CCL4, CCL20, CXCL8, CXCL9, CXCL10, CXCL11) in response to in vitro co-culture with anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) via IFNγ and TNFα. Furthermore, T-cell-derived IFNγ inhibits CXCL12 secretion by CAFs in vitro. Our results highlight the ability of T-cell effector cytokines to modulate the CAF secretome in NSCLC.

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.