| Literature DB >> 30012670 |
Te-Chia Wu1,2, Kangling Xu1, Jan Martinek1,2,3, Robyn R Young4, Romain Banchereau1, Joshy George2, Jacob Turner1, Kyung In Kim2, Sandra Zurawski1, Xuan Wang1, Derek Blankenship1, Hannah M Brookes2, Florentina Marches1,2, Gerlinde Obermoser1, Elizabeth Lavecchio1, Maren K Levin1, Sookyoung Bae2, Cheng-Han Chung1,2,3, Jennifer L Smith1, Alma-Martina Cepika1, Kyp L Oxley1, George J Snipes5, Jacques Banchereau1,2, Virginia Pascual1, Joyce O'Shaughnessy6, A Karolina Palucka7,2.
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. ©2018 American Association for Cancer Research.Entities:
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Year: 2018 PMID： 30012670 PMCID： PMC6391892 DOI： 10.1158/0008-5472.CAN-18-0413
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701