Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker.

Autor:	Berszin M; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Michaelides I; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany.; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany., Siemert J; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Röhl L; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Wellhausen J; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Wald T; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Bohr C; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany., Künzel J; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany., Gradistanac T; Department of Pathology, University Hospital Leipzig, Leipzig, Germany., Dietz A; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Zebralla V; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Pirlich M; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Wiegand S; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany., Wichmann G; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Feb 28; Vol. 12, pp. 795277. Date of Electronic Publication: 2022 Feb 28 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.795277
Abstrakt:	Background: Pembrolizumab and cetuximab are antibodies under investigation in head and neck squamous cell carcinoma (HNSCC) either as single agents or combined with cisplatin and other chemotherapeutic drugs, e.g., 5-fluorouracil and/or docetaxel. However, also the combination of both antibodies may have potential in recurrent/metastatic (R/M) HNSCC, in particular in cisplatin-resistant or -refractory cases or patients with comorbid disease, e.g. patients with impaired renal function. Methods: To clarify potential benefit that may result from such combination, we used the FLAVINO assay, a short-time ex vivo assay to compare responsiveness of HNSCC to pembrolizumab, cetuximab and both combined regarding colony formation of epithelial cells of biopsy-derived tumor samples and their cytokine production within three days either without or with stimulation with 10 ng/mL interferon gamma (IFN-γ). Vascular endothelial growth factor A (VEGF), monocyte chemoattractant protein 1 (MCP-1 or CCL2), interleukin 6 (IL-6), IL-8, IFN-γ, and interferon gamma-induced protein 10 (IP-10 or CXCL10) in supernatants were measured by ELISA. Results: We detected huge heterogeneity in response to cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation. Moreover, we detected a link between IFN-γ induced IP-10 release and improved outcome in those HNSCC patients who were capable to respond to IFN-γ and pembrolizumab, cetuximab and both combined with a further increase in IP-10 production. We derived an "IP-10 score" that independent from clinical characteristics of HNSCC patients and therapy regimens applied was able to predict their outcome. Conclusions: The heterogeneity in the ex vivo response of cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation identifies subgroups of HNSCC patients with deviating OS. Competing Interests: AD and SW received honoraria for invited lectures from MSD. AD received funding from MSD for an investigator-initiated clinical trial (ADRISK, ClinicalTrials.gov, no. NCT03480672). 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. (Copyright © 2022 Berszin, Michaelides, Siemert, Röhl, Wellhausen, Wald, Bohr, Künzel, Gradistanac, Dietz, Zebralla, Pirlich, Wiegand and Wichmann.)
Databáze:	MEDLINE
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