IGF1R Axis Inhibition Restores Dendritic Cell Antitumor Response in Ovarian Cancer
| Autor: | S. Hantisteanu, Mordechai Hallak, Gabriel M. Groisman, Ofer Limonad, Shilhav Meisel-Sharon, Ilan Bruchim, Lina Somri-Gannam |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Original article endocrine system diseases medicine.medical_treatment lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Immune system medicine Insulin-like growth factor 1 receptor business.industry Growth factor Monocyte Dendritic cell medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens female genital diseases and pregnancy complications body regions 030104 developmental biology medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Ovarian cancer business |
| Zdroj: | Translational Oncology Translational Oncology, Vol 13, Iss 8, Pp 100790-(2020) |
| ISSN: | 1936-5233 |
| Popis: | Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in several malignancies, including ovarian cancer. IGF1R targeting showed antiproliferative activity of EOC cells. However, clinical studies failed to show significant benefit. EOC cells suppress antitumor immune responses by inducing dendritic cell (DC) dysfunction. The IGF1 axis can regulate DC maturation. The current study evaluated involvement of the IGF1 axis in DC differentiation in EOC. Studies were conducted on EOC and on a human monocyte cell line. Tissue microarray analysis (TMA) was performed on 36 paraffin blocks from EOC patients. Expression of IGF1R, p53, Ki67, BRCA1, and DC markers was evaluated using immunohistochemistry. Co-culture of EOC cells with DC pretreated with IGF1R inhibitor blocked cancer cell migration. TMA demonstrated higher rate of IGF1R protein expression in patients with advanced (76.9%) as compared to early (40%) EOC. A negative correlation between IGF1R protein expression and the CD1c marker was found. These findings provide evidence that IGF1R axis inhibition could be a therapeutic strategy for ovarian cancer by restoring DC-mediated antitumor immunity. |
| Databáze: | OpenAIRE |
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