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RSS FeedsIJMS, Vol. 20, Pages 4693: EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells (International Journal of Molecular Sciences)

 
 

22 september 2019 16:02:29

 
IJMS, Vol. 20, Pages 4693: EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells (International Journal of Molecular Sciences)
 


The adverse prognosis of most patients with ovarian cancer is related to recurrent disease caused by resistance to chemotherapeutic and targeted therapeutics. Besides their direct activity against tumor cells, monoclonal antibodies and tyrosine kinase inhibitors (TKIs) also influence the antitumoral activity of immune cells, which has important implications for the design of immunotherapies. In this preclinical study, we treated different ovarian cancer cell lines with anti-epidermal growth factor receptor (EGFR) TKIs and co-incubated them with natural killer (NK) cells. We studied treatment-related structural and functional changes on tumor and immune cells in the presence of the anti-EGFR antibody cetuximab and investigated NK-mediated antitumoral activity. We show that long-term exposure of ovarian cancer cells to TKIs leads to reduced responsiveness of intrinsically sensitive cancer cells over time. Inversely, neither long-term treatment with TKIs nor cetuximab could overcome the intrinsic resistance of certain ovarian cancer cells to anti-EGFR agents. Remarkably, tumor cells pretreated with anti-EGFR TKIs showed increased sensitivity towards NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In contrast, the cytokine secretion of NK cells was reduced by TKI sensitization. Our data suggest that sensitization of tumor cells by anti-EGFR TKIs differentially modulates interactions with NK cells. These data have important implications for the design of chemo-immuno combination therapies in this tumor entity.


 
218 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 20, Pages 4695: Sphingosine 1-Phosphate Receptor Blockade Affects Pro-Inflammatory Bone Marrow-Derived Macrophages and Relieves Mouse Fatty Liver Injury (International Journal of Molecular Sciences)
IJMS, Vol. 20, Pages 4702: CRISPR/Cas9-Based Mutagenesis of Starch Biosynthetic Genes in Sweet Potato (Ipomoea Batatas) for the Improvement of Starch Quality (International Journal of Molecular Sciences)
 
 
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