Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma.

Autor:	Lyu SI; Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany., Johannsen J; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Simon AG; Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany., Knipper K; Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany., Wuerdemann N; 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., Sharma SJ; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Thelen M; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Hansen KK; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Fretter C; Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany., Klasen C; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Esser J; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Suchan MC; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Abing H; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Zimmermann PH; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Schultheis AM; Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany., Schloesser HA; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany., Klussmann JP; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Quaas A; Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany., Eckel HNC; Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2024 Jan 24; Vol. 12, pp. 1337361. Date of Electronic Publication: 2024 Jan 24 (Print Publication: 2024).
DOI:	10.3389/fcell.2024.1337361
Abstrakt:	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. FAP high and PDGFRb high 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 PDGFRb low periostin low α-SMA low 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. Competing Interests: HS: Funding for Research by Astra Zeneca and Tabby therapeutics; SAB for BMS. JK: Honoraria for advisory boards from BMS, MSD, for invited talks from Astra Zeneca, BMS, MSD, Merck and financial support for research projects from MSD. HE: Honoraria for advisory boards from MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Lyu, Johannsen, Simon, Knipper, Wuerdemann, Sharma, Thelen, Hansen, Fretter, Klasen, Esser, Suchan, Abing, Zimmermann, Schultheis, Schloesser, Klussmann, Quaas and Eckel.)
Databáze:	MEDLINE
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