TNF Counterbalances the Emergence of M2 Tumor Macrophages

Franz Kratochvill, Geoffrey Neale, Jessica M. Haverkamp, Lee Ann Van de Velde, Amber M. Smith, Daisuke Kawauchi, Justina McEvoy, Martine F. Roussel, Michael A. Dyer, Joseph E. Qualls, Peter J. Murray

Research output: Contribution to journalArticlepeer-review

212 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1902-1914
Number of pages13
JournalCell Reports
Issue number11
StatePublished - Sep 22 2015

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'TNF Counterbalances the Emergence of M2 Tumor Macrophages'. Together they form a unique fingerprint.

Cite this