EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Anti-EGFR Sensitization of Ovarian Cancer Cells Enhanced Tumor Cell Viability and Increased Resistance to Cetuximab
2.2. Sensitization with Anti-EGFR TKI Decreased Sensitivity to FasLigand but Enhanced Ovarian Cancer Cells for NK Cell-Mediated Cytotoxic Degranulation
2.3. Anti-EGFR TKI Sensitized Ovarian Cancer Cells Led to Reduced Cytokine Release of Secretory NK Cells
2.4. Anti-EGFR Sensitized Ovarian Cancer Cells Show Altered Expression of Stress-Induced Ligands and MHC I and Enhanced Cytokine Release
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Cell Culture
4.2. Sensitization of Ovarian Cancer Cells with Anti-EGFR TKIs
4.3. MTT Proliferation Assay
4.4. Isolation of NK Cells of Healthy Donors
4.5. ELISA for Human IL18, IL12, and TNFα
4.6. Antibodies Used for Flow Cytometric Analysis (FACS)
4.7. Extracellular and Intracellular FACS Staining
4.8. CD107a Degranulation Assay
4.9. 7-AAD/Annexin Staining
4.10. ELISpot for IFNγ Detection
4.11. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Mallmann-Gottschalk, N.; Sax, Y.; Kimmig, R.; Lang, S.; Brandau, S. EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells. Int. J. Mol. Sci. 2019, 20, 4693. https://doi.org/10.3390/ijms20194693
Mallmann-Gottschalk N, Sax Y, Kimmig R, Lang S, Brandau S. EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells. International Journal of Molecular Sciences. 2019; 20(19):4693. https://doi.org/10.3390/ijms20194693
Chicago/Turabian StyleMallmann-Gottschalk, Nina, Yvonne Sax, Rainer Kimmig, Stephan Lang, and Sven Brandau. 2019. "EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells" International Journal of Molecular Sciences 20, no. 19: 4693. https://doi.org/10.3390/ijms20194693