Frontiers in Cell and Developmental Biology (Jan 2024)
Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma
- Su Ir Lyu,
- Jannik Johannsen,
- Jannik Johannsen,
- Adrian Georg Simon,
- Karl Knipper,
- Nora Wuerdemann,
- Shachi Jenny Sharma,
- Shachi Jenny Sharma,
- Martin Thelen,
- Kevin Karl Hansen,
- Kevin Karl Hansen,
- Caroline Fretter,
- Charlotte Klasen,
- Charlotte Klasen,
- Julia Esser,
- Julia Esser,
- Malte Christian Suchan,
- Malte Christian Suchan,
- Helen Abing,
- Helen Abing,
- Philipp Heinrich Zimmermann,
- Philipp Heinrich Zimmermann,
- Anne Maria Schultheis,
- Hans Anton Schloesser,
- Hans Anton Schloesser,
- Jens Peter Klussmann,
- Jens Peter Klussmann,
- Alexander Quaas,
- Hans Nikolaus Caspar Eckel,
- Hans Nikolaus Caspar Eckel
Affiliations
- Su Ir Lyu
- Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
- Jannik Johannsen
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Jannik Johannsen
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Adrian Georg Simon
- Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
- Karl Knipper
- Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany
- Nora Wuerdemann
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Shachi Jenny Sharma
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Shachi Jenny Sharma
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Martin Thelen
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Kevin Karl Hansen
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Kevin Karl Hansen
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Caroline Fretter
- Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
- Charlotte Klasen
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Charlotte Klasen
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Julia Esser
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Julia Esser
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Malte Christian Suchan
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Malte Christian Suchan
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Helen Abing
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Helen Abing
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Philipp Heinrich Zimmermann
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Philipp Heinrich Zimmermann
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Anne Maria Schultheis
- Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
- Hans Anton Schloesser
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Hans Anton Schloesser
- Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany
- Jens Peter Klussmann
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Jens Peter Klussmann
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- Alexander Quaas
- Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
- Hans Nikolaus Caspar Eckel
- Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany
- Hans Nikolaus Caspar Eckel
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- DOI
- https://doi.org/10.3389/fcell.2024.1337361
- Journal volume & issue
-
Vol. 12
Abstract
Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration.Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed.Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006).Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.
Keywords
- oropharyngeal cancer
- human papillomavirus
- head and neck squamous cell carcinoma
- platelet-derived growth factor receptor beta
- alpha smooth muscle actin
- periostin