Oncostatin M signalling orchestrates immune remodelling and metabolism within the breast tumour microenvironment

Cancer and inflammation are closely related in a bidirectional manner, with chronic inflammation considered an intrinsic feature of cancer. Oncostatin M (OSM) is an inflammatory cytokine that belongs to the interleukin-6 cytokine family and is involved in processes such as inflammatory response, regeneration, and metabolism. The data presented in this thesis demonstrate that OSM promotes the remodelling of the immune system and metabolic reprogramming in breast cancer. We observe that OSM, secreted by myeloid cells, promotes the infiltration of macrophages and neutrophils and is associated with dysfunctional factors affecting the action of cytotoxic T cells, which are the main effectors of antitumor function. We have proposed mechanisms involving cytokines or immune checkpoint receptors as mediators of these OSM effects. Additionally, we observe that OSM promotes extracellular matrix remodelling in the tumour and a more glycolytic metabolism in both tumour cells and tumour-associated fibroblasts, effects that are closely linked to immune infiltration remodelling. All these data support that inhibiting the OSM signalling pathway could be a promising therapeutic target, in combination with immunotherapy, for breast cancer patients.