Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages

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 d...

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Vydáno v:	Oncoimmunology Ročník 6; číslo 8; s. e1334744
Hlavní autoři:	Kersten, Kelly, Coffelt, Seth B., Hoogstraat, Marlous, Verstegen, Niels J.M., Vrijland, Kim, Ciampricotti, Metamia, Doornebal, Chris W., Hau, Cheei-Sing, Wellenstein, Max D., Salvagno, Camilla, Doshi, Parul, Lips, Esther H., Wessels, Lodewyk F.A., de Visser, Karin E.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Taylor & Francis 03.08.2017 Taylor & Francis Group
Témata:	Breast cancer CCL2 immunosuppression neutrophils Original Research tumor-associated macrophages tumor-induced inflammation γδ T cells γδ T cells tumor-induced inflammation CCL2 immunosuppression Breast cancer neutrophils tumor-associated macrophages
ISSN:	2162-402X, 2162-4011, 2162-402X
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Supplemental data for this article can be accessed on the publisher's website. Current address: Cancer Research UK Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.
ISSN:	2162-402X 2162-4011 2162-402X
DOI:	10.1080/2162402X.2017.1334744