Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0209073 on July 15, 2009

Published online before print July 15, 2009
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(Journal of Leukocyte Biology. 2009;86:1105-1109.)
© 2009 Society for Leukocyte Biology

Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages

Robert D. Stout*,1, Stephanie K. Watkins{dagger} and Jill Suttles*

* Department of Microbiology and Immunology, University of Louisville School of Medicine and James Graham Brown Cancer Center, Louisville, Kentucky, USA; and
{dagger} Cancer and Inflammation Program, Tumor Immunity and Tolerance Section, Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick, Frederick, Maryland, USA

1. Correspondence: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA. E-mail: bobstout{at}louisville.edu

ABSTRACT

The extent to which the functional heterogeneity of M{varphi}s is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that M{varphi}s are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This "functional plasticity" hypothesis predicts that the functionally polarized M{varphi}s in chronic pathologies do not represent M{varphi} sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAM{varphi}s are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAM{varphi}s in situ, reducing M{varphi} support of tumor growth and metastasis and enhancing M{varphi} proimmunogenic activities. Increased knowledge of how M{varphi} function is regulated and how polarized M{varphi}s can be reprogrammed in situ will increase our ability to control M{varphi} function in a variety of pathological states, including cancer and chronic inflammatory disease.

Key Words: macrophage subsets • cancer • IL-12 • inflammation




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