Title

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

Document Type

Article

Publication Date

7-16-2018

JAX Source

Cancer Res 2018 Jul 16 [Epub ahead of print]

PMID

30012670

DOI

https://doi.org/10.1158/0008-5472.CAN-18-0413

Grant

CA034196, The Jackson Laboratory

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).

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