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Cell Rep. 2015 Sep 22;12(11):1902-14. doi: 10.1016/j.celrep.2015.08.033. Epub 2015 Sep 10.

TNF Counterbalances the Emergence of M2 Tumor Macrophages.

Author information

1
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
5
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: joseph.qualls@cchmc.org.
6
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: peter.murray@stjude.org.

Abstract

Cancer can involve non-resolving, persistent inflammation where varying numbers of tumor-associated macrophages (TAMs) infiltrate and adopt different activation states between anti-tumor M1 and pro-tumor M2 phenotypes. Here, we resolve a cascade causing differential macrophage phenotypes in the tumor microenvironment. Reduction in TNF mRNA production or loss of type I TNF receptor signaling resulted in a striking pattern of enhanced M2 mRNA expression. M2 gene expression was driven in part by IL-13 from eosinophils co-recruited with inflammatory monocytes, a pathway that was suppressed by TNF. Our data define regulatory nodes within the tumor microenvironment that balance M1 and M2 populations. Our results show macrophage polarization in cancer is dynamic and dependent on the balance between TNF and IL-13, thus providing a strategy for manipulating TAMs.

PMID:
26365184
PMCID:
PMC4581986
DOI:
10.1016/j.celrep.2015.08.033
[Indexed for MEDLINE]
Free PMC Article

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