TNF Counterbalances the Emergence of M2 Tumor Macrophages

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1902-1914
Number of pages13
JournalCell Reports
Volume12
Issue number11
DOIs
StatePublished - Sep 22 2015

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Macrophages
Tumors
Neoplasms
Tumor Microenvironment
Interleukin-13
Phenotype
Messenger RNA
Tumor Necrosis Factor Receptors
Eosinophils
Gene expression
Monocytes
Chemical activation
Polarization
Inflammation
Gene Expression
Population

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kratochvill, F., Neale, G., Haverkamp, J. M., Van de Velde, L. A., Smith, A., Kawauchi, D., ... Murray, P. J. (2015). TNF Counterbalances the Emergence of M2 Tumor Macrophages. Cell Reports, 12(11), 1902-1914. https://doi.org/10.1016/j.celrep.2015.08.033

TNF Counterbalances the Emergence of M2 Tumor Macrophages. / Kratochvill, Franz; Neale, Geoffrey; Haverkamp, Jessica M.; Van de Velde, Lee Ann; Smith, Amber; Kawauchi, Daisuke; McEvoy, Justina; Roussel, Martine F.; Dyer, Michael A.; Qualls, Joseph E.; Murray, Peter J.

In: Cell Reports, Vol. 12, No. 11, 22.09.2015, p. 1902-1914.

Research output: Contribution to journalArticle

Kratochvill, F, Neale, G, Haverkamp, JM, Van de Velde, LA, Smith, A, Kawauchi, D, McEvoy, J, Roussel, MF, Dyer, MA, Qualls, JE & Murray, PJ 2015, 'TNF Counterbalances the Emergence of M2 Tumor Macrophages', Cell Reports, vol. 12, no. 11, pp. 1902-1914. https://doi.org/10.1016/j.celrep.2015.08.033
Kratochvill F, Neale G, Haverkamp JM, Van de Velde LA, Smith A, Kawauchi D et al. TNF Counterbalances the Emergence of M2 Tumor Macrophages. Cell Reports. 2015 Sep 22;12(11):1902-1914. https://doi.org/10.1016/j.celrep.2015.08.033
Kratochvill, Franz ; Neale, Geoffrey ; Haverkamp, Jessica M. ; Van de Velde, Lee Ann ; Smith, Amber ; Kawauchi, Daisuke ; McEvoy, Justina ; Roussel, Martine F. ; Dyer, Michael A. ; Qualls, Joseph E. ; Murray, Peter J. / TNF Counterbalances the Emergence of M2 Tumor Macrophages. In: Cell Reports. 2015 ; Vol. 12, No. 11. pp. 1902-1914.
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