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HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-236220
- Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal–epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, weHead and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal–epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient’s sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.…
Autor(en): | Verena Boschert, Jonas Teusch, Anwar Aljasem, Philipp Schmucker, Nicola Klenk, Anton Straub, Max BittrichORCiD, Axel SeherORCiD, Christian Linz, Urs D. A. Müller-Richter, Stefan Hartmann |
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URN: | urn:nbn:de:bvb:20-opus-236220 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 21 |
Heft / Ausgabe: | 20 |
Aufsatznummer: | 8770 |
Originalveröffentlichung / Quelle: | International Journal of Molecular Sciences (2020) 21:22, 8770. https://doi.org/10.3390/ijms21228770 |
DOI: | https://doi.org/10.3390/ijms21228770 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | HGF; HNSCC; Met; PD-L1; head and neck cancer; immune therapy |
Datum der Freischaltung: | 11.05.2021 |
Open-Access-Publikationsfonds / Förderzeitraum 2020 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |