Breast cancer is one of the deadliest cancers in women and especially the aggressive subtypes such as triple-negative breast cancer (TNBC) are difficult to treat. Although the immune system provides a natural barrier against invading and metastasizing breast tumor cells, it often fails to halt the disease progression due to immunosuppressive activity orchestrated by breast tumor cells and surrounding stromal cells. The protein chitinase 3-like 1 (CHI3L1) has been highlighted as a potential immunotherapeutic target in cancer due to its stimulation of immunosuppression and metastasis, but its role in breast cancer and more specifically TNBC, remains to be unraveled. This project will investigate the involvement of CHI3L1 signaling in TNBC progression, lymphatic development and dissemination as well as inflammation of triple-negative breast tumors using an in-house characterized immunocompetent intraductal mouse model and clinical samples from TNBC patients. We will also examine the therapeutic effect of CHI3L1 blockade and assess whether such inhibition synergistically enhances the clinical efficacy of immunotherapeutic treatments in TNBC. The results of this project will unequivocally demonstrate if CHI3L1 blockade can be used as an effective TNBC treatment strategy, potentially in combination with other immunotherapies, providing a response to the high clinical demand for better TNBC therapeutics.