Berszin, Michael and Michaelides, Ioannis and Siemert, Julia and Roehl, Louisa and Wellhausen, Jana and Wald, Theresa and Bohr, Christopher and Kuenzel, Julian and Gradistanac, Tanja and Dietz, Andreas and Zebralla, Veit and Pirlich, Markus and Wiegand, Susanne and Wichmann, Gunnar (2022) 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. FRONTIERS IN ONCOLOGY, 12: 795277. ISSN 2234-943X,
Full text not available from this repository. (Request a copy)Abstract
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-gamma). Vascular endothelial growth factor A (VEGF), monocyte chemoattractant protein 1 (MCP-1 or CCL2), interleukin 6 (IL-6), IL-8, IFN-gamma, 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-gamma stimulation. Moreover, we detected a link between IFN-gamma induced IP-10 release and improved outcome in those HNSCC patients who were capable to respond to IFN-gamma 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-gamma stimulation identifies subgroups of HNSCC patients with deviating OS.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CD80 COSTIMULATORY MOLECULE; IFN-GAMMA; COLONY FORMATION; SUPPRESSES HEAD; MURINE MODEL; SINGLE-ARM; OPEN-LABEL; EXPRESSION; RESISTANCE; PD-1; interferon-gamma induced protein 10 (IP-10); CXCL10 (C-X-C motif ligand 10); interferon-gamma (IFN-gamma); vascular endothelial growth factor A (VEGF); interleukin 6 (IL-6); head and neck squamous cell carcinoma (HNSCC); ex vivo chemo-sensitivity assay; colony formation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Feb 2024 15:29 |
| Last Modified: | 20 Feb 2024 15:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57721 |
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