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IFN γ and TNF α drive an inflammatory secretion profile in cancer‐associated fibroblasts from human non‐small cell lung cancer

2025/01/01 by Lilian Koppensteiner, Layla Mathieson, Liam Neilson +2 · 1 voice
Immunology and Microbiology · Medicine · #Cancer Cells and Metastasis #Immune cells in cancer #Immunotherapy and Immune Responses

paper · pdf · doi:10.1002/1873-3468.15083

openalex publication_date 2025/01/01 · openalex created_date 2025/01/02 · openalex updated_date 2026/07/31

Abstract

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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