Triple-negative breast cancer (TNBC) is one of the deadliest and difficult to treat breast cancer subtypes in women. Although the immune system provides a natural barrier against these tumors, it often fails in its task due to immunosuppression orchestrated by the tumor cells and accompanying stromal cells. The inflammatory protein chitinase 3-like 1 (CHI3L1) has been identified in my junior postdoc project as a potential immunotherapeutic target in TNBC that fuels immunosuppressive activity. This senior postdoc project introduces a second inflammatory protein lipocalin 2 (LCN2) as an additional immunotherapeutic target in TNBC, with a potentially similar immunosuppressive and tumor-stimulating role as CHI3L1. More specifically, I will investigate the involvement of either the separate and the combined CHI3L1 and LCN2 signaling in TNBC progression and tumor inflammation using an immunocompetent intraductal mouse model and clinical samples from TNBC patients. I will also examine the therapeutic effect of separate versus combined CHI3L1 and LCN2 blockade and assess whether a combined inhibition enhances the clinical efficacy of immunotherapeutic treatments in TNBC. The results of this project will unequivocally demonstrate if combining CHI3L1 and LCN2 blockade can be used as an effective TNBC treatment strategy, potentially combined and synergizing with other immunotherapies, providing a response to the clinical demand for improved TNBC therapeutics.