Introduction The insulin-like growth factor 1 receptor (IGF1R) plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC), therefore is regarded as a promising therapeutic target. Recently, it has been shown that IGF1 can regulate dendritic cell (DC) maturation and T cell activation. Our study aims to investigate the combination effect of IGF1R inhibition and anti-PD-1 treatment on EOC.

Methods EOC cell lines were co-cultured with IGF1R inhibitor (AEW-541)-treated-DCs. DC differentiation and EOC proliferation levels were evaluated by Flow Cytometry Assay (FACS). C57BL/6 mice with established peritoneal ovarian cancer were injected with single or combined anti-PD-1 and AEW-541 treatment, and their survival was evaluated. conventional DCs and T-cell population levels were analyzed by FACS. Finally, RNA was extracted from tumors and RNA sequencing was performed.

Results IGF1R inhibitor treatment significantly induced DC differentiation in AEW-541 pre-treated-DCs compared to control after 24 h. In addition, Differentiated AEW-541-treated-DCs significantly decreased EOC cell proliferation. In vivo experiment showed that combined anti-PD-1/IGF1R treatment decreased tumor weight compared to single treatments. Moreover, the anti-PD-1/IGF1R treatment significantly increased the conventional DCs compared to AEW-541 and anti-PD-1 treatments. The Gene Ontology (GO) analysis indicate that the most significant differential biological process terms were immune response by increased lymphocytes cells activation.

Conclusion/Implications IGF1R pathway inhibition in differentiated DCs suppressed EOC cell proliferation. IGF1R inhibitor combined with anti-PD-1 may result in enhanced anti-tumor activity. Thus, restoring the anti-tumor immune response by IGF1R targeting in combination with immunotherapy may be an effective therapy for EOC.