IGF2BP1 promotes the immune escape in advanced stage ovarian cancer

The mRNA binding protein IGF2BP1 (IGF2 mRNA binding protein) is an oncofetal protein de novo synthesized in various aggressive solid cancers. In the cytoplasm, the protein controls the localization, translation and/or turnover of target mRNAs and thereby modulates cell proliferation, migration and invasion during development and cancer. In epithelial ovarian carcinoma (EOC) high levels of IGF2BP1 expression are significantly correlated with poorer prognosis and associated with the mesenchymal subtype of EOC, characterized by a reduced immune signature.
Aiming to characterize the role of IGF2BP1 in EOC we used a combination of deep sequencing and quantitative proteomics. As expected we identified the protein as an essential regulator of cell migration and invasion. More strikingly, an IGF2BP1-dependent modulation of components of the MHC class I antigen processing and presentation machinery (APM) was found in EOC-derived cells, which is in line with the frequent deficiencies in these molecules in EOC lesions. IGF2BP1 repressed the expression of genes essential for MHC class I antigen processing machinery leading to an impaired MHC class I surface antigen expression. Additionally, IGF2BP1 promoted CD274/PD-L1 expression which itself represses the proliferation of activated T-cells. In summary, our data suggest that IGF2BP1 promotes the immune escape of invasive cancer cells in advanced stage ovarian cancer.