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Science. 2014 May 23;344(6186):921-5. doi: 10.1126/science.1252510. Epub 2014 May 8.

The cellular and molecular origin of tumor-associated macrophages.

Author information

1
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
2
New York Genome Center, New York, NY 10022, USA.
3
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
4
Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA.
5
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. lim@mskcc.org.

Abstract

Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases, including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an "alternatively activated" phenotype. TAM terminal differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.

PMID:
24812208
PMCID:
PMC4204732
DOI:
10.1126/science.1252510
[Indexed for MEDLINE]
Free PMC Article

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