Who am I? (re‐)Defining fibroblast identity and immunological function in the age of bioinformatics

Fletcher, Anne L.; Turley, Shannon J.

doi:10.1111/imr.12993

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Given the data showing that CAF contribute to regulating tumor immunity (11,12,48), we investigated the different ligands expressed by CAF populations found in human NSCLC (Fig. 4A).…”

Section: Adh1b + Caf and Fap + Caf Correlate With Immune Cell Composi...mentioning

confidence: 99%

Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors

et al. 2022

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It is currently accepted that cancer-associated fibroblasts (CAF) participate in T-cell exclusion from tumor nests. To unbiasedly test this, we used single-cell RNA sequencing coupled with multiplex imaging on a large cohort of lung tumors. We identified four main CAF populations, of which two are associated with T-cell exclusion: (i) MYH11+aSMA+ CAF, which are present in early-stage tumors and form a single-cell layer lining cancer aggregates, and (ii) FAP+aSMA+ CAF, which appear in more advanced tumors and organize in patches within the stroma or in multiple layers around tumor nests. Both populations orchestrate a particular structural tissue organization through dense and aligned fiber deposition compared to T cell permissive CAF. Yet they produce distinct matrix molecules, including collagen IV (MYH11+aSMA+ CAF) and collagen XI/XII (FAP+aSMA+ CAF). Hereby, we uncovered unique molecular programs of CAF driving T cell marginalization, whose targeting should increase immunotherapy efficacy in patients bearing T cell-excluded tumors.

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“…Given the data showing that CAF contribute to regulating tumor immunity (11,12,48), we investigated the different ligands expressed by CAF populations found in human NSCLC (Fig. 4A).…”

Section: Adh1b + Caf and Fap + Caf Correlate With Immune Cell Composi...mentioning

confidence: 99%

Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors

et al. 2022

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“…When it starts, ECCs possibly expose on the surface adhesion molecules, such as cadherins, integrins, connexins, and others [36] and their contact with neighboring cells and immune cells and CAFs form, possibly, synapse-like connections. Physical cell-cell communication between fibroblasts and other cell types can influence their chemical communication with immune cells [36,124]. There is only indirect evidence for the formation of synapse-like structures between CAFs and cancer and immune cells.…”

Section: Fibroblasts Immune and Cancer Cells Interactionsmentioning

confidence: 99%

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

Alekseenko,

Zhukova,

Kondratyeva

et al. 2024

Preprint

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52 years have passed since President Nixon launched the "War on Cancer". The goals outlined by the President were not achieved because cancer treatment applied such as chemotherapy, radiotherapy, and targeted therapy have not fully met expectations. We suggest a new chemotherapeutic strategy: disrupting the communication between cancer cells and their microenvironment by chemical means. Immunological synapses that form between cancer cells and immune or other stromal cells provide an attractive target for this approach. Synapses form ligand-receptor clusters within interface of the interacting cells. Despite their differences, synapses share common properties: intercellular protein clusters; the proximity of these proteins; and their cooperative interaction making a synapse an unified functional unit. Synapses provide the limited space for the focused intercellular exchange of signaling molecules and particles. Therefore, destruction of synapses is expected to cause collapse of various tumor types. Additionally, the clustered arrangement of synapse components offers opportunities to increase treatment safety by reducing the concentration of cell impermeable agents used, to enhance its specificity applying cross-linking reagents, thus restricting modifications of surface-exposed molecules. By attaching a cleavable cell permeable toxic agent to a crosslinker should further enhance a killing potential in treating cancer. The proposed approach promises to be simple, universal, and less expensive than existing cancer therapy methods.

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“…For example, proin ammatory broblasts are consistently detected across many mouse and human diseases from keloid lesions 18 to aged skin 19 , brotic Dupuytren's nodules 20 , and atopic dermatitis 12 . Functionally, these cells modulate the immune response via production of proin ammatory cytokines 3,[21][22] . Single cell RNA-seq studies have also reported transcriptional differences between broblasts taken from different wound regions 6,9,23 .…”

Section: Introductionmentioning

confidence: 99%

CD201+ fascia progenitors choreograph injury repair

Rinkevich

Correa-Gallegos

et al. 2022

Preprint

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Optimal tissue recovery and organismal survival1 are achieved by tight spatiotemporal tuning of tissue inflammation, contraction and scar-formation. Here, we discover a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using murine skin injury models, single-cell transcriptomics, and genetic lineage tracing and ablation models, we demonstrate that CD201+ progenitors pace wound healing by generating multiple specialized cell types from proinflammatory fibroblasts to myofibroblasts in a spatiotemporally tuned sequence. We identify retinoic acid and hypoxia signaling as differentiation checkpoints that control the graduated entry of fascia progenitor into the proinflammatory and myofibroblast states. Modulating their differentiation, with retinoic acid and hypoxia-inducible factor 1-alpha, or genetically ablating this cellular lineage, impaired the graduated appearances of specialized fibroblasts and chronically delayed wound healing. The discovery of fascia progenitors, their microenvironment, and the signaling pathways that control the graduated transitions thereof provides a new roadmap to understand and clinically treat impaired wound healing.

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Who am I? (re‐)Defining fibroblast identity and immunological function in the age of bioinformatics

Abstract: leagues 2 highlight the extraordinary advances made possible in this field through the strategic use of gene-targeting and lineage-tracing mouse models, and more recently by single-cell transcriptomics. An array of Cre-reporter mice and mice with inducible expression of Cre

Cited by 5 publications

References 18 publications

Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors

Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

CD201+ fascia progenitors choreograph injury repair

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