iCAF signaling in PDAC

In contrast to myCAFs, a subpopulation of αSMA-low CAFs with high IL6 secretion was observed distant from tumour epithelium and from myCAFs [56]. This subpopulation was activated by paracrine signalling from tumour cells as demonstrated in a Transwell system (which allows paracrine interactions between organoids and PSCs but blocks direct contact between the two cell types). Single-cell transcriptome analysis revealed upregula- tion of cytokines (IL6, IL11, LIF) and chemokines (CXCL1, CXCL2) in this subpopulation and they were therefore termed inflammatory CAFs (iCAFs) (Figure 1). Gene set enrichment analysis identified upregulation of inflammatory signalling pathways such as IFNγ response, TNF/NFκB, IL2/STAT5, IL6/JAK/STAT3, and the complement pathway in iCAFs in human PDAC . Exploring the Biology of Cancer-Associated Fibroblasts in Pancreatic Cancer. Bryce AS, Dreyer SB, Froeling FEM, Chang DK. Cancers (Basel). 2022 Oct 28;14(21):5302. doi: 10.3390/cancers14215302. PMID: 3635872