"Re-educating" tumor-associated macrophages by targeting NF-kappa B
File(s)
Author(s)
Type
Journal Article
Abstract
The nuclear factor κB (NF-κB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-κB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive “alternative” phenotype that requires IκB kinase β–mediated NF-κB activation. When NF-κB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a “classically” activated phenotype; IL-12high, major histocompatibility complex IIhigh, but IL-10low and arginase-1low. Targeting NF-κB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12–dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to “re-educate” the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies.
Date Issued
2008-06-09
ISSN
0022-1007
Publisher
Rockefeller Univ Press
Start Page
1261
End Page
1268
Journal / Book Title
Journal of Experimental Medicine
Volume
205
Issue
6
Copyright Statement
© 2008 Hagemann et al. The Rockefeller University Press.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000257002000004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
NITRIC-OXIDE SYNTHASE
OVARIAN-CANCER CELLS
MOUSE MODEL
INFLAMMATION
ALPHA
ACTIVATION
LIPOPOLYSACCHARIDE
IMMUNOTHERAPY
INVASIVENESS
PROGRESSION
Animals
Cell Differentiation
Humans
Immunosuppression
Macrophages
Mice
NF-kappa B
Neoplasms
Phenotype
Signal Transduction
11 Medical And Health Sciences
Publication Status
Published