TNF Counterbalances the Emergence of M2 Tumor Macrophages

被引：222

作者：

Kratochvill, Franz ^{[1
,2
]}

Neale, Geoffrey ^{[3
]}

Haverkamp, Jessica M. ^{[1
,2
]}

Van de Velde, Lee-Ann ^{[1
,2
]}

Smith, Amber M. ^{[1
,2
]}

Kawauchi, Daisuke ^{[5
]}

McEvoy, Justina ^{[4
]}

Roussel, Martine F. ^{[5
]}

Dyer, Michael A. ^{[4
]}

Qualls, Joseph E. ^{[1
,2
]}

Murray, Peter J. ^{[1
,2
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[3] St Jude Childrens Res Hosp, Hartwell Ctr Biotechnol & Bioinformat, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[5] St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Memphis, TN 38105 USA

来源：

CELL REPORTS | 2015年 / 12卷 / 11期

基金：

奥地利科学基金会;

关键词：

NF-KAPPA-B; CANCER PROGRESSION; ADIPOSE-TISSUE; MICROENVIRONMENT; INHIBITION; CELLS; POLARIZATION; ACTIVATION; PHENOTYPE; REVEALS;

D O I：

10.1016/j.celrep.2015.08.033

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 protumor 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.

引用

页码：1902 / 1914

页数：13

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