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.
CXCL10 (C-X-C motif ligand 10)
colony formation
ex vivo chemo-sensitivity assay
head and neck squamous cell carcinoma (HNSCC)
interferon-gamma (IFN-γ)
interferon-gamma induced protein 10 (IP-10)
interleukin 6 (IL-6)
vascular endothelial growth factor A (VEGF)
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2022
2022
Historique:
received:
14
10
2021
accepted:
19
01
2022
entrez:
17
3
2022
pubmed:
18
3
2022
medline:
18
3
2022
Statut:
epublish
Résumé
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. To clarify potential benefit that may result from such combination, we used the FLAVINO assay, a short-time 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. The heterogeneity in the
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
To clarify potential benefit that may result from such combination, we used the FLAVINO assay, a short-time
Results
UNASSIGNED
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
UNASSIGNED
The heterogeneity in the
Identifiants
pubmed: 35296001
doi: 10.3389/fonc.2022.795277
pmc: PMC8918678
doi:
Types de publication
Journal Article
Langues
eng
Pagination
795277Informations de copyright
Copyright © 2022 Berszin, Michaelides, Siemert, Röhl, Wellhausen, Wald, Bohr, Künzel, Gradistanac, Dietz, Zebralla, Pirlich, Wiegand and Wichmann.
Déclaration de conflit d'intérêts
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.
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