Peio Azcoaga Azcoaga – Investigador predoctoral en IIS Biodonostia.

Salón de Actos-IIS Biodonostia.



Currently there are not efficient therapies with curative intent for advanced breast cancer (BC). In particular, advanced triple negative (TN) BC has poor prognosis and lacks targeted therapies. Therefore, finding new strategies for those cases is an unmet need with high clinical impact. In this context, the pro-inflammatory cytokine Oncostatin M (OSM), along with its downstream pathway, is a promising therapeutic target as it is over-expressed in this tumour subtype and its activation promotes invasiveness, in addition to the reprogramming of the tumour microenvironment (TME) composition by acting upon tumour cells and fibroblasts. Here we hypothesized whether OSM could be mediating a malignant metabolic phenotype within the TME that could lead to immune suppression. In order to obtain mechanistic insights, we analysed the transcriptomes of publicly available patients’ datasets along with different cell types that compose the tumour, upon OSM stimulation. Metabolic reprogramming-related genes were found to be altered by OSM and were afterwards validated by RT-qPCR, Western Blotting and functional assays. These metabolic genes were also differentially detected in an orthotopic BC mouse model combining CAFs and BC cells, validating the in vivo repercussion of our findings. This work sheds light on the role of OSM in BC progression, which could be mediated by the promotion of a malignant metabolism and immunosuppression, supporting that the OSM pathway could be a promising candidate for therapeutic targeting in BC.