IFNγ and TNFα Drive an Inflammatory Secretion Profile in Cancer-associated Fibroblasts from Human Non-small Cell Lung Cancer

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2025 Jan 1

PMID 39743376

Authors

Lilian Koppensteiner

Layla Mathieson

Liam Neilson

Richard A OConnor

Ahsan R Akram

Affiliations

Soon will be listed here.

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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