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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

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.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84568
Date05 April 2023
CreatorsBerszin, 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
PublisherFrontiers Research Foundation
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation2234-943X, 795277

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