The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer

With the rise of immunotherapies as a treatment option for various cancers, there is a critical need to understand the mechanisms through which cancers evade the immune system. In a subset of poor outcome Triple Negative Breast Cancers, cytotoxic T cells are excluded from the tumor nest and restricted to the surrounding stroma, a phenomenon known as stromal restriction. Data from genetically engineered mouse models and human tumors identified that the secreted cytokine Chitinase-3 like 1 regulates the spatial positioning of T cells in several tumor types including breast, lung and colon. We further demonstrate that Chi3l1 regulates the spatial exclusion of T cells through the direct induction and deposition of neutrophil extracellular traps. Given the importance T cell infiltration in the immune elimination of nascent tumors, the future targeting of Chi3l1 should improve immunotherapy efficacy and outcomes in patients with tumors characterized by a T cell excluded microenvironment. Overall design: MIC mice were induced with doxyxycline in their drinking water (2mg/mL). The hyperplastic mammary gland was harvested.RNA was extracted and sequenced