Print Email Facebook Twitter Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages Title Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages Author Kersten, Kelly (Netherlands Cancer Institute) Coffelt, Seth B. (Netherlands Cancer Institute) Hoogstraat, Marlous (Netherlands Cancer Institute; University Medical Center Utrecht) Verstegen, Niels J.M. (Netherlands Cancer Institute) Vrijland, Kim (Netherlands Cancer Institute) Ciampricotti, Metamia (Netherlands Cancer Institute) Doornebal, Chris W. (Netherlands Cancer Institute; Amsterdam UMC) Hau, Cheei-Sing (Netherlands Cancer Institute) Wellenstein, Max D. (Netherlands Cancer Institute) Salvagno, Camilla (Netherlands Cancer Institute) Doshi, Parul (Janssen Research and Development) Lips, Esther H. (Netherlands Cancer Institute) Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics) de Visser, Karin E. (Netherlands Cancer Institute) Date 2017 Abstract Patients with primary solid malignancies frequently exhibit signs of systemic inflammation. Notably, elevated levels of neutrophils and their associated soluble mediators are regularly observed in cancer patients, and correlate with reduced survival and increased metastasis formation. Recently, we demonstrated a mechanistic link between mammary tumor-induced IL17-producing γδ T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation in a genetically engineered mouse model for invasive breast cancer. How tumors orchestrate this systemic inflammatory cascade to facilitate dissemination remains unclear. Here we show that activation of this cascade relies on CCL2-mediated induction of IL1β in tumor-associated macrophages. In line with these findings, expression of CCL2 positively correlates with IL1Β and macrophage markers in human breast tumors. We demonstrate that blockade of CCL2 in mammary tumor-bearing mice results in reduced IL17 production by γδ T cells, decreased neutrophil expansion and enhanced CD8+ T cell activity. These results highlight a new role for CCL2 in facilitating the breast cancer-induced pro-metastatic systemic inflammatory γδ T cell–IL17–neutrophil axis. Subject Breast cancerCCL2immunosuppressionneutrophilstumor-associated macrophagestumor-induced inflammationγδ T cells To reference this document use: http://resolver.tudelft.nl/uuid:d2685dea-2dbf-460f-81f9-603e31ea6804 DOI https://doi.org/10.1080/2162402X.2017.1334744 ISSN 2162-4011 Source OncoImmunology, 6 (8) Part of collection Institutional Repository Document type journal article Rights © 2017 Kelly Kersten, Seth B. Coffelt, Marlous Hoogstraat, Niels J.M. Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W. Doornebal, Cheei-Sing Hau, Max D. Wellenstein, Camilla Salvagno, Parul Doshi, Esther H. Lips, L.F.A. Wessels, Karin E. de Visser Files PDF 38239340.pdf 2.46 MB Close viewer /islandora/object/uuid:d2685dea-2dbf-460f-81f9-603e31ea6804/datastream/OBJ/view