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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84568 |
| Date | 05 April 2023 |
| Creators | 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 | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2234-943X, 795277 |
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