IL-1 receptor antagonist controls transcriptional signature of inflammation in patients with metastatic breast cancer.

Te-Chia Wu
Kangling Xu
Jan Martinek, The Jackson Laboratory
Robyn R Young
Romain Banchereau
Joshy George, The Jackson Laboratory
Jacob Turner
Kyung In Kim, The Jackson Laboratory
Sandra Zurawski
Xuan Wang
Derek Blankenship
Hannah M Brookes
Florentina Marches, The Jackson Laboratory
Gerlinde Obermoser
Elizabeth Lavecchio
Maren K Levin
Sookyoung Bae
Cheng-Han Chung, The Jackson Laboratory
Jennifer L Smith
Alma-Martina Cepika
Kyp L Oxley
George J Snipes
Jacques Banchereau, The Jackson Laboratory
Virginia Pascual
Joyce O'Shaughnessy
Karolina Palucka, 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).