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Five CAF populations (CAF S1–S5) are defined, including the novel CAF-S5 marked by FAP and PDPN expression without αSMA. CAF-S1 or CAF-S5 presence associates with worse survival after curative resection, consistent with poor-prognosis patterns in TCGA datasets.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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is the study’s main purpose regarding CAF subtypes in NSCLC?","Question",{"text":63,"@type":64},"To identify CAF subtypes present in NSCLC, focus on the novel CAF-S5 population, and evaluate how these subtypes relate to patient survival outcomes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were CAF subtypes detected and categorized in this research?",{"text":68,"@type":64},"Primary NSCLC resections were analyzed using flow cytometry and multiplex immunofluorescence for fibroblast activation markers, enabling identification of CAF subsets.",{"name":70,"@type":61,"acceptedAnswer":71},"What defines the novel CAF-S5 population, and how does it affect prognosis?",{"text":72,"@type":64},"CAF-S5 expresses FAP and PDPN but lacks αSMA, and its presence correlates with worse survival even after curative 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Journal of Cancer  \nARTICLE OPEN   \nCellular and Molecular Biology  \nCancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome  \nLayla Mathieson 1,2, Lilian Koppensteiner 1,2, David A. Dorward3, Richard A. O’Connor 1,2 and Ahsan R. Akram 1,2,4 ✉  \n© The Author(s) 2024  \n|  |  |  |\n| --- | --- | --- |\n|  | BACKGROUND: Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC) . Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC.\u003Cbr>METHODS: Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets.\u003Cbr>RESULTS: We identified five CAF populations, termed CAF S1-S5 . CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types. CONCLUSION: This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| subset where its presence correlates to worse survival outcome. |  |  |\n|  | British Journal of Cancer (2024) 130:1758–1769; [https://doi.org/10.1038/s41416-024-02671-1](https://doi.org/10.1038/s41416-024-02671-1) |  |\n|  |  |  |\n\nBACKGROUND  \nLung cancer is the leading cause of cancer death globally [1] and non-small cell lung cancer (NSCLC) accounts for ~85% of cases [2] . Current NSCLC therapies are often unsuccessful, with drug resistance leading to treatment failure and disease progression [3] . The tumour stroma plays a role in this resistance to therapy and has emerged as an important target for therapies to combat cancers such as NSCLC [4–7] .  \nOne of the most common cell types of the tumour stroma is the cancer-associated fibroblast (CAF) [8] . In health, fibroblasts are a quiescent structural component of the extracellular matrix (ECM), which become activated in response to wound signalling. In their activated state they produce ECM components, and engage in crosstalk with immune cells to promote wound healing [9] . CAFs are irreversibly activated, have an enhanced migratory phenotype over normal activated fibroblasts, a greater proliferative ability and an enhanced secretome [10] . CAFs also have roles in immune evasion, metastasis, invasion, angiogenesis and resistance to drug treatment [6, 11–15] .  \nSeveral studies have shown that CAFs represent a heterogeneous population composed of functionally distinct subtypes [6, 16–21] . The phenotype of these subtypes has been characterised in some solid organ malignancies, including breast, ovarian, pancreatic and lung cancers [17, 19–23] . Markers frequently used to distinguish these subtypes include α-smooth muscle actin (αSMA), fibroblast activation protein (FAP), podoplanin (PDPN), integrin β1 (CD29) and fibroblast-specific protein-1  \n(FSP-1) . Two key subtypes of note, commonly termed CAF-S1 and CAF-S4, have been identified in several studies, CAF-S1 display a FAP-hi phenotype associated with adhesion, wound healing and immunosuppression while CAF-S4 which are FAP-low/nega","cbCaiodXTUCziljG","https://ap.wps.com/l/cbCaiodXTUCziljG","pdf",5271488,12,"English","# Background\n## Cancer-associated fibroblasts in NSCLC\n# Methods\n## NSCLC patient sample processing\n# Results\n## Identification of CAF subtypes (CAF S1–S5)\n# Conclusion\n## Prognostic importance of CAF-S5","[{\"question\":\"What is the study’s main purpose regarding CAF subtypes in NSCLC?\",\"answer\":\"To identify CAF subtypes present in NSCLC, focus on the novel CAF-S5 population, and evaluate how these subtypes relate to patient survival outcomes.\"},{\"question\":\"How were CAF subtypes detected and categorized in this research?\",\"answer\":\"Primary NSCLC resections were analyzed using flow cytometry and multiplex immunofluorescence for fibroblast activation markers, enabling identification of CAF subsets.\"},{\"question\":\"What defines the novel CAF-S5 population, and how does it affect prognosis?\",\"answer\":\"CAF-S5 expresses FAP and PDPN but lacks αSMA, and its presence correlates with worse survival even after curative resection.\"}]","Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome | PDF",1789996794]