Koppensteiner Lilian, Mathieson Layla, Neilson Liam, O'Connor Richard A, Akram Ahsan R
Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, UK.
Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, The University of Edinburgh, UK.
FEBS Lett. 2025 Mar;599(5):713-723. doi: 10.1002/1873-3468.15083. Epub 2025 Jan 1.
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.
癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）中的主要非恶性成分。在实体瘤中，CAFs表现出高度的肿瘤间和肿瘤内异质性，尽管CAF亚群的驱动因素尚未完全了解。在此，我们证明，与抗CD3/抗CD28刺激的外周血单核细胞（PBMCs）进行体外共培养时，非小细胞肺癌（NSCLC）患者来源的CAFs通过IFNγ和TNFα上调炎性细胞因子（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。我们的结果突出了T细胞效应细胞因子调节NSCLC中CAF分泌组的能力。
