The cellular and molecular origin of tumor-associated macrophages Journal Article
| Authors: | Franklin, R. A.; Liao, W.; Sarkar, A.; Kim, M. V.; Bivona, M. R.; Liu, K.; Pamer, E. G.; Li, M. O. |
| Article 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. |
| Keywords: | signal transduction; nonhuman; cell proliferation; tumor associated leukocyte; animal cell; mouse; phenotype; animals; mice; mus; immune system; vascular cell adhesion molecule 1; animal experiment; animal model; inflammation; notch receptor; cell differentiation; cell line, tumor; mice, inbred c57bl; receptors, notch; cytotoxic t lymphocyte; molecular analysis; monocyte; tumor growth; tumor; disease control; macrophage; macrophages; monocyte-macrophage precursor cells; ontogeny; mammary neoplasms, animal; vascular cell adhesion molecule-1; female; priority journal; article; mammary tissue macrophage |
| Journal Title: | Science |
| Volume: | 344 |
| Issue: | 6186 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2014-05-23 |
| Start Page: | 921 |
| End Page: | 925 |
| Language: | English |
| DOI: | 10.1126/science.1252510 |
| PROVIDER: | scopus |
| PUBMED: | 24812208 |
| PMCID: | PMC4204732 |
| DOI/URL: | |
| Notes: | Science -- Cited By (since 1996):1 -- Export Date: 8 July 2014 -- CODEN: SCIEA -- Source: Scopus |
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