IL-1 receptor antagonist controls transcriptional signature of inflammation in patients with metastatic breast cancer.
Cancer Res 2018 Jul 16 [Epub ahead of print]
CA034196, The Jackson Laboratory
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).
Wu, Te-Chia; Xu, Kangling; Martinek, Jan; Young, Robyn R; Banchereau, Romain; George, Joshy; Turner, Jacob; Kim, Kyung In; Zurawski, Sandra; Wang, Xuan; Blankenship, Derek; Brookes, Hannah M; Marches, Florentina; Obermoser, Gerlinde; Lavecchio, Elizabeth; Levin, Maren K; Bae, Sookyoung; Chung, Cheng-Han; Smith, Jennifer L; Cepika, Alma-Martina; Oxley, Kyp L; Snipes, George J; Banchereau, Jacques; Pascual, Virginia; O'Shaughnessy, Joyce; and Palucka, Karolina, "IL-1 receptor antagonist controls transcriptional signature of inflammation in patients with metastatic breast cancer." (2018). Faculty Research Ahead of Print. 89.