Grotz, Melanie ; Gijzel, Lieke van ; Bitsch, Peter ; Carrara, Stefania C. ; Kolmar, Harald ; Garg, Sakshi (2024)
Mimicking the immunosuppressive impact of fibroblasts in a 3D multicellular spheroid model.
In: Frontiers in Drug Discovery, 2024, 4
doi: 10.26083/tuprints-00027873
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
Targeting the tumor microenvironment (TME) is an attractive strategy for cancer therapy, as tumor cells in vivo are surrounded by many different influential cell types, with complex interactions strongly affecting tumor progression and therapeutic outcome. Cancer-associated fibroblasts (CAFs) represent an abundant stromal cell type in the TME that modulate tumor development by exerting an immunosuppressive effect to influence effector immune cell activation. One promising target for TME-directed therapy is the CAF marker fibroblast activation protein-α (FAP). In this study, we employ a multicellular three-dimensional (3D) spheroid model, including tumor cells, fibroblast cells, and naïve T cells and could observe a protective effect of fibroblasts on tumor cells. Subsequently, we demonstrate that fibroblasts express FAP at differing expression levels in two-dimensional (2D) versus 3D cells. Lastly, we show that in a triple-culture of tumor cells, T cells and fibroblasts, the simultaneous assembly of fibroblasts using the high-affinity ligand oncoFAP with an engineered α-CD3-scFv-Fc-dextran-oncoFAP construct resulted in effective T cell activation to augment immunogenicity. Overall, this model can be routinely used for preclinical screening to study the effects of fibroblasts on the TME in vitro.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Grotz, Melanie ; Gijzel, Lieke van ; Bitsch, Peter ; Carrara, Stefania C. ; Kolmar, Harald ; Garg, Sakshi |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Mimicking the immunosuppressive impact of fibroblasts in a 3D multicellular spheroid model |
| Sprache: | Englisch |
| Publikationsjahr: | 16 September 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 26 Juli 2024 |
| Ort der Erstveröffentlichung: | Lausanne |
| Verlag: | Frontiers Media S.A. |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in Drug Discovery |
| Jahrgang/Volume einer Zeitschrift: | 4 |
| Kollation: | 16 Seiten |
| DOI: | 10.26083/tuprints-00027873 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/27873 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Targeting the tumor microenvironment (TME) is an attractive strategy for cancer therapy, as tumor cells in vivo are surrounded by many different influential cell types, with complex interactions strongly affecting tumor progression and therapeutic outcome. Cancer-associated fibroblasts (CAFs) represent an abundant stromal cell type in the TME that modulate tumor development by exerting an immunosuppressive effect to influence effector immune cell activation. One promising target for TME-directed therapy is the CAF marker fibroblast activation protein-α (FAP). In this study, we employ a multicellular three-dimensional (3D) spheroid model, including tumor cells, fibroblast cells, and naïve T cells and could observe a protective effect of fibroblasts on tumor cells. Subsequently, we demonstrate that fibroblasts express FAP at differing expression levels in two-dimensional (2D) versus 3D cells. Lastly, we show that in a triple-culture of tumor cells, T cells and fibroblasts, the simultaneous assembly of fibroblasts using the high-affinity ligand oncoFAP with an engineered α-CD3-scFv-Fc-dextran-oncoFAP construct resulted in effective T cell activation to augment immunogenicity. Overall, this model can be routinely used for preclinical screening to study the effects of fibroblasts on the TME in vitro. |
| Freie Schlagworte: | 3D cell culture, spheroid formation, tumor microenvironment, cancer-associated fibroblasts, fibroblast activation protein-α, T cells, immunosuppressive, in vitro |
| ID-Nummer: | Artikel-ID: 1427407 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-278731 |
| Zusätzliche Informationen: | This article is part of the Research Topic: Next Generation Micro-Physiological Systems for Pragmatic Use in Regular Industrial Workflow Sec. Technologies and Strategies to Enable Drug Discovery |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 16 Sep 2024 11:28 |
| Letzte Änderung: | 17 Sep 2024 05:22 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Mimicking the immunosuppressive impact of fibroblasts in a 3D multicellular spheroid model. (deposited 16 Sep 2024 11:28) [Gegenwärtig angezeigt]
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