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PMID: 24812208 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The cellular and molecular origin of tumor-associated macrophages.

Science (New York, N.Y.) ·Vol. 344 ·No. 6186 ·2014-05-23 ·Pages 921-5

Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG, Li MO

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.

MeSH Terms
Animals Cell Differentiation Cell Line, Tumor Cell Proliferation Female Inflammation/immunology,pathology Macrophages/immunology Mammary Neoplasms, Animal/immunology,pathology Mice Mice, Inbred C57BL Monocyte-Macrophage Precursor Cells/immunology Receptors, Notch/metabolism Signal Transduction Vascular Cell Adhesion Molecule-1/metabolism
Chemicals
Receptors, Notch Vascular Cell Adhesion Molecule-1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Franklin Ruth A
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.
Liao Will
New York Genome Center, New York, NY 10022, USA.
Sarkar Abira
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
Kim Myoungjoo V
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.
Bivona Michael R
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
Liu Kang
Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA.
Pamer Eric G
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
Li Ming O
Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. lim@mskcc.org.
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1252510
Email
lim@mskcc.org
Published
2014-05-23
Epub
2014-00-08
Pages
921-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4204732
Subset
IM
Grants
NCI NIH HHS · P30 CA008748 · United States
NIAID NIH HHS · R01 AI101251 · United States
NIAID NIH HHS · R37 AI039031 · United States
NIAID NIH HHS · AI101251 · United States
Databases
GEO
GSE56755
Corrections
CommentIn
PMID: 24855239
CommentIn
PMID: 25220733
External Links
PubMed source DOI: 10.1126/science.1252510 PMC Full Text View journal details
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