| Title | IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Wu T-C, Xu K, Martinek J, Young RR, Banchereau R, George J, Turner J, Kim KIn, Zurawski S, Wang X, Blankenship D, Brookes HM, Marches F, Obermoser G, Lavecchio E, Levin MK, Bae S, Chung C-H, Smith JL, Cepika A-M, Oxley KL, Snipes GJ, Banchereau J, Pascual V, O'Shaughnessy J, A Palucka K |
| Journal | Cancer Res |
| Volume | 78 |
| Issue | 18 |
| Pagination | 5243-5258 |
| Date Published | 2018 09 15 |
| ISSN | 1538-7445 |
| Keywords | Animals, Breast Neoplasms, Capecitabine, CD11c Antigen, Cell Line, Tumor, Cell Membrane, Female, Furans, Gene Expression Regulation, Neoplastic, Humans, Inflammation, Interleukin 1 Receptor Antagonist Protein, Interleukin-1beta, Ketones, Leukocytes, Mononuclear, Macrophages, Mice, Mice, SCID, Myeloid Cells, Neoplasm Metastasis, Neoplasm Transplantation, Paclitaxel, Pilot Projects, Transcription, Genetic, Transforming Growth Factor beta |
| 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). IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist. . |
| DOI | 10.1158/0008-5472.CAN-18-0413 |
| Custom 1 | |
| Alternate Journal | Cancer Res. |
| PubMed ID | 30012670 |
| PubMed Central ID | PMC6391892 |
| Grant List | P30 CA034196 / CA / NCI NIH HHS / United States |