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Supplementary figures from IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer

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posted on 2023-03-31, 02:06 authored by Te-Chia Wu, Kangling Xu, Jan Martinek, Robyn R. Young, Romain Banchereau, Joshy George, Jacob Turner, Kyung In Kim, Sandra Zurawski, Xuan Wang, Derek Blankenship, Hannah M. Brookes, Florentina Marches, Gerlinde Obermoser, Elizabeth Lavecchio, Maren K. Levin, Sookyoung Bae, Cheng-Han Chung, Jennifer L. Smith, Alma-Martina Cepika, Kyp L. Oxley, George J. Snipes, Jacques Banchereau, Virginia Pascual, Joyce O'Shaughnessy, A. Karolina Palucka

Figure S1. Cytokines screening from breast tumor tissue Figure S2. IL-1β induces TSLP production from breast cancer cells. Figure S3. IL-1β production in DCs is caspase-1 dependent. Figure S4. IL-1β production requires TAK1-dependent caspase-1 activation. Figure S5. IL-1 and TGF-β mediate tumor-promoting type 2 cytokines in humanized mouse model. Figure S6. Cells component in blood from patients in clinical trial. Anakinra signature clustered breast cancer patients in TCGA dataset.

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ARTICLE 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 AACR.See related commentary by Dinarello, p. 5200

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    Cancer Research

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    Breast CancerImmunologyImmunotherapyProgression, Invasion & MetastasisInflammation and tumor development

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