title: The cellular and molecular origin of tumor-associated macrophages.
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.
authors.affiliation: 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.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Franklin
authors.affiliation: New York Genome Center, New York, NY 10022, USA.
authors.forename: Will
authors.initials: W
authors.lastname: Liao
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
authors.forename: Abira
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: 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.
authors.forename: Myoungjoo V
authors.initials: MV
authors.lastname: Kim
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bivona
authors.affiliation: Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. lim@mskcc.org.
authors.forename: Ming O
authors.initials: MO
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055017:Monocyte-Macrophage Precursor Cells / Q000276:immunology; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D051880:Receptors, Notch; D019010:Vascular Cell Adhesion Molecule-1