IL-1 receptor antagonist controls transcriptional signature of inflammation in patients with metastatic breast cancer.
Abstract
Inflammation affects tumor immune surveillance and resistance to therapy. However, no approved treatments aimed at decreasing chronic tumor-associated inflammation are available, largely due to incomplete understanding of pathogenesis. Here we show that production of interleukin (IL)-1β in primary breast cancer (BC) tumors is linked to advanced disease and originates from tumor-infiltrating CD11c+ myeloid cells. IL-1β production was triggered by cancer cell membrane-derived TGF-β, and neutralizing TGF-β or IL-1 receptor prevented BC progression in a humanized mouse model. Patients with metastatic HER2-negative BC displayed a transcriptional signature of inflammation in the blood leukocytes, which was attenuated by IL-1 blockade. When present in primary BC tumors, this signature discriminated patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC).