Cetuximab-induced natural killer cell cytotoxicity in head and neck squamous cell carcinoma cell lines: investigation of the role of cetuximab sensitivity and HPV status

Autor: Jorrit De Waele, Marc Peeters, Evelien Smits, Filip Lardon, Jan B Vermorken, Julie Jacobs, Hasan Baysal, An Wouters, Patrick Pauwels, Hannah Zaryouh, Ines De Pauw
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Cancer Research
Cell
Cetuximab
chemical and pharmacologic phenomena
Innate lymphoid cells
Cell Growth Processes
Article
Natural killer cell
03 medical and health sciences
0302 clinical medicine
Targeted therapies
Antineoplastic Agents
Immunological
Cell Line
Tumor
Medicine
Humans
Epidermal growth factor receptor
Cytotoxicity
Head and neck cancer
neoplasms
Papillomaviridae
030304 developmental biology
Antibody-dependent cell-mediated cytotoxicity
0303 health sciences
biology
business.industry
Squamous Cell Carcinoma of Head and Neck
Papillomavirus Infections
Antibody-Dependent Cell Cytotoxicity
medicine.disease
Head and neck squamous-cell carcinoma
digestive system diseases
ErbB Receptors
Killer Cells
Natural
Cancer therapeutic resistance
medicine.anatomical_structure
Oncology
Head and Neck Neoplasms
030220 oncology & carcinogenesis
biology.protein
Cancer research
Human medicine
Antibody
business
medicine.drug
Zdroj: British Journal of Cancer
The British journal of cancer
ISSN: 1532-1827
0007-0920
Popis: Background The epidermal growth factor receptor (EGFR) is overexpressed by 80–90% of squamous cell carcinoma of head and neck (HNSCC). In addition to inhibiting EGFR signal transduction, cetuximab, a monoclonal antibody targeting EGFR can also bind to fragment crystallisable domain of immunoglobulins G1 present on natural killer (NK), causing antibody-dependent cellular cytotoxicity (ADCC). However, presence of cetuximab resistance limits effective clinical management of HNSCC. Methods In this study, differences in induction of ADCC were investigated in a panel of ten HNSCC cell lines. Tumour cells were co-cultured with NK cells and monitored using the xCELLigence RTCA. Results While ADCC was not influenced by HPV status, hypoxia and cetuximab resistance did affect ADCC differentially. Intrinsic cetuximab-resistant cell lines showed an increased ADCC induction, whereas exposure to hypoxia reduced ADCC. Baseline EGFR expression was not correlated with ADCC. In contrast, EGFR internalisation following cetuximab treatment was positively correlated with ADCC. Conclusion These findings support the possibility that resistance against cetuximab can be overcome by NK cell-based immune reactions. As such, it provides an incentive to combine cetuximab with immunotherapeutic approaches, thereby possibly enhancing the anti-tumoural immune responses and achieving greater clinical effectiveness of EGFR-targeting agents.
Databáze: OpenAIRE
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