IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer.

Abstract:

:Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c+ myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGFβ. Neutralizing TGFβ or IL1 receptor prevents breast cancer progression in humanized mouse model. Patients with metastatic HER2- breast cancer display a transcriptional signature of inflammation in the blood leukocytes, which is attenuated after IL1 blockade. When present in primary breast cancer tumors, this signature discriminates patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC).Significance: IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist. Cancer Res; 78(18); 5243-58. ©2018 AACRSee related commentary by Dinarello, p. 5200.

journal_name

Cancer Res

journal_title

Cancer research

authors

Wu TC,Xu K,Martinek J,Young RR,Banchereau R,George J,Turner J,Kim KI,Zurawski S,Wang X,Blankenship D,Brookes HM,Marches F,Obermoser G,Lavecchio E,Levin MK,Bae S,Chung CH,Smith JL,Cepika AM,Oxley KL,Snipes GJ,B

doi

10.1158/0008-5472.CAN-18-0413

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

5243-5258

issue

18

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-18-0413

journal_volume

78

pub_type

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