| Title: |
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 |
| Authors: |
Berszin, Michael; Michaelides, Ioannis; Siemert, Julia; Röhl, Louisa; Wellhausen, Jana; Wald, Theresa; Bohr, Christopher; Künzel, Julian; Gradistanac, Tanja; Dietz, Andreas; Zebralla, Veit; Pirlich, Markus; Wiegand, Susanne; Wichmann, Gunnar |
| Publisher Information: |
Frontiers Research Foundation |
| Publication Year: |
2022 |
| Collection: |
Universität Leipzig: Qucosa |
| Subject Terms: |
interferon-gamma induced protein 10 (IP-10); CXCL10 (C-X-C motif ligand 10); interferon-gamma (IFN-g); vascular endothelial growth factor A (VEGF); interleukin 6 (IL-6); head and neck squamous cell carcinoma (HNSCC); ex vivo chemo-sensitivity assay; colony formation; info:eu-repo/classification/ddc/610; ddc:610 |
| Description: |
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-g). Vascular endothelial growth factor A (VEGF), monocyte chemoattractant protein 1 (MCP-1 or CCL2), interleukin 6 (IL-6), IL-8, IFN-g, 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-g stimulation. Moreover, we detected a link between IFN-g induced IP-10 release and improved outcome in those HNSCC patients who were capable to respond to IFN-g 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-g stimulation identifies subgroups of HNSCC patients with deviating OS. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2234-943X |
| Relation: |
795277; https://ul.qucosa.de/id/qucosa%3A84568 |
| Availability: |
https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-845683; https://ul.qucosa.de/id/qucosa%3A84568; https://ul.qucosa.de/api/qucosa%3A84568/attachment/ATT-0/ |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.F49909EC |
| Database: |
BASE |