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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1410447
IGF1R inhibition and PD-1 blockade improve anti-tumor immune response in epithelial ovarian cancer
Provisionally accepted- 1 Hillel Yaffe Medical Center, Hadera, Israel
- 2 Sackler Faculty of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Tel Aviv, Israel
Introduction: The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC) and is considered a promising therapeutic target. EOC is an immunosuppressive disease, although there are limited data about the involvement of the IGF1R system in the anti-tumor immune response in the EOC microenvironment. Methods: In the current study, we hypothesized that IGF 1 receptor (IGF1R) involvement in the maturation of dendritic cells (DC) with the co-inhibition of IGF1R and PD-1 would affect the EOC microenvironment. Results: We found that DC pretreated with IGF1R inhibitor resulted in fewer EOC cells. Moreover, in vivo experiments conducted with an EOC mouse model, with anti-PD-1/IGF1R combined, resulted in lower tumor weight compared to individual treatments. Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1. The combined treatment increased CD8+ T-cell levels compared to AEW-541 alone. RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone. Discussion: These findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations.
Keywords: insulin-like growth factor-1 receptor, epithelial ovarian cancer, Immunotherapy, Dendritic Cells, PD-1, Immune System
Received: 02 May 2024; Accepted: 10 Sep 2024.
Copyright: © 2024 Somri Gannam, Meisel Sharon, Hantisteanu, Bar-Noy, Sigal, Groisman, Hallak, Werner and Bruchim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ilan Bruchim, Hillel Yaffe Medical Center, Hadera, Israel
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