Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer

Cords, Lena; Engler, Stefanie; Haberecker, Martina; Rüschoff, Jan Hendrik; Moch, Holger; de Souza, Natalie; Bodenmiller, Bernd

doi:10.1016/j.ccell.2023.12.021

Cited by 51 publications

(8 citation statements)

References 80 publications

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“…While recently published CAF-focused studies performed using IMC platform report detection of various CAF populations ( 30 , 50 , 51 ), in our work we were able to identify a broader spectrum of different CAF subsets. Differently to the panel reported by Tornaas et al.…”

Section: Discussionmentioning

confidence: 57%

Development of 42 marker panel for in-depth study of cancer associated fibroblast niches in breast cancer using imaging mass cytometry

Røgenes,

Finne,

Winge

et al. 2024

Front. Immunol.

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Imaging Mass Cytometry (IMC) is a novel, and formidable high multiplexing imaging method emerging as a promising tool for in-depth studying of tissue architecture and intercellular communications. Several studies have reported various IMC antibody panels mainly focused on studying the immunological landscape of the tumor microenvironment (TME). With this paper, we wanted to address cancer associated fibroblasts (CAFs), a component of the TME very often underrepresented and not emphasized enough in present IMC studies. Therefore, we focused on the development of a comprehensive IMC panel that can be used for a thorough description of the CAF composition of breast cancer TME and for an in-depth study of different CAF niches in relation to both immune and breast cancer cell communication. We established and validated a 42 marker panel using a variety of control tissues and rigorous quantification methods. The final panel contained 6 CAF-associated markers (aSMA, FAP, PDGFRa, PDGFRb, YAP1, pSMAD2). Breast cancer tissues (4 cases of luminal, 5 cases of triple negative breast cancer) and a modified CELESTA pipeline were used to demonstrate the utility of our IMC panel for detailed profiling of different CAF, immune and cancer cell phenotypes.

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Section: Discussionmentioning

confidence: 57%

Development of 42 marker panel for in-depth study of cancer associated fibroblast niches in breast cancer using imaging mass cytometry

Røgenes,

Finne,

Winge

et al. 2024

Front. Immunol.

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“…Taken together, characterization of the immune cell networks underlying the inflammatory structure allows to identify the impact of cells on the cellular network beyond its direct cellular neighborhood allowing a deeper understanding of the underlying pathomechanisms. These insights can then be used to identify the mechanism of action of drugs ( 15 ), predict therapy resistance in patients ( 55 ) and predict outcome prognosis ( 56 , 57 ).…”

Section: Discussionmentioning

confidence: 99%

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation

Friedel,

Pierre,

Kolbinger

et al. 2024

Front. Immunol.

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IntroductionDuring an innate inflammation, immune cells form distinct pro- and anti-inflammatory regions around pathogen-containing core-regions. Mast cells are localized in an anti-inflammatory microenvironment during the resolution of an innate inflammation, suggesting antiinflammatory roles of these cells.MethodsHigh-content imaging was used to investigated mast cell-dependent changes in the regional distribution of immune cells during an inflammation, induced by the toll-like receptor (TLR)-2 agonist zymosan.ResultsThe distance between the zymosan-containing core-region and the anti-inflammatory region, described by M2-like macrophages, increased in mast cell-deficient mice. Absence of mast cells abolished dendritic cell (DC) activation, as determined by CD86-expression and localized the DCs in greater distance to zymosan particles. The CD86- DCs had a higher expression of the pro-inflammatory interleukins (IL)-1β and IL-12/23p40 as compared to activated CD86+ DCs. IL-4 administration restored CD86 expression, cytokine expression profile and localization of the DCs in mast cell-deficient mice. The IL-4 effects were mast cell-specific, since IL-4 reduction by eosinophil depletion did not affect activation of DCs.DiscussionWe found that mast cells induce DC activation selectively at the site of inflammation and thereby determine their localization within the inflammation. Overall, mast cells have antiinflammatory functions in this inflammation model and limit the size of the pro-inflammatory region surrounding the zymosan-containing core region.

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“…S8 ). A recent study identified CAF subsets in NSCLC by utilising multiplexed imaging mass cytometry and included the key markers we used [ 48 ]. Although their analysis does not allow direct comparison to our study to identify CAF-S1 or CAF-S5, they did identify a favourable outcome with SMA CAFs which align with our CAF-S4.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome

Mathieson,

Koppensteiner,

Dorward

et al. 2024

Br J Cancer

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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. 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. 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 subset where its presence correlates to worse survival outcome.

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Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer

Cited by 51 publications

References 80 publications

Development of 42 marker panel for in-depth study of cancer associated fibroblast niches in breast cancer using imaging mass cytometry

Development of 42 marker panel for in-depth study of cancer associated fibroblast niches in breast cancer using imaging mass cytometry

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation

Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome

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