TY - JOUR
T1 - IGF1R Axis Inhibition Restores Dendritic Cell Antitumor Response in Ovarian Cancer
AU - Somri-Gannam, Lina
AU - Meisel-Sharon, Shilhav
AU - Hantisteanu, Shay
AU - Groisman, Gabriel
AU - Limonad, Ofer
AU - Hallak, Mordechai
AU - Bruchim, Ilan
N1 - Funding Information:
This research was funded by the Israel Cancer Research Foundation , Montreal, Canada, grant number 2026011 , and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Institute of Technology , Haifa, Israel, to Dr. Ilan Bruchim.
Funding Information:
This work was performed in partial fulfillment of the requirements for a PhD degree by Lina Somri-Gannam at the Gynecology Laboratory, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Israel. The support of the Israel Cancer Research Foundation (grant 2026011 to I.B.) is kindly acknowledged. In addition, the authors wish to thank the support of The Ruth and Bruce Rappaport Faculty of Medicine , Technion, Haifa, Israel. Finally, we wish to thank the director of the histopathology laboratory at Haemek Medical Center, Shulamit Goez, and Natalia Edison for their major help with the TMA analysis.
Funding Information:
This work was performed in partial fulfillment of the requirements for a PhD degree by Lina Somri-Gannam at the Gynecology Laboratory, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Israel. The support of the Israel Cancer Research Foundation (grant 2026011 to I.B.) is kindly acknowledged. In addition, the authors wish to thank the support of The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. Finally, we wish to thank the director of the histopathology laboratory at Haemek Medical Center, Shulamit Goez, and Natalia Edison for their major help with the TMA analysis. The authors declare no conflict of interest. This research was funded by the Israel Cancer Research Foundation, Montreal, Canada, grant number 2026011, and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Institute of Technology, Haifa, Israel, to Dr. Ilan Bruchim.
Publisher Copyright:
© 2020 The Authors
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85084644148&partnerID=8YFLogxK
U2 - 10.1016/j.tranon.2020.100790
DO - 10.1016/j.tranon.2020.100790
M3 - Article
C2 - 32428851
AN - SCOPUS:85084644148
SN - 1944-7124
VL - 13
JO - Translational Oncology
JF - Translational Oncology
IS - 8
M1 - 100790
ER -
