The Cellular and Molecular Origin of Tumor-associated Macrophages

Overview

Journal Science

Specialty Science

Date 2014 May 10

PMID 24812208

Citations 722

Authors

Ruth A Franklin

Will Liao

Abira Sarkar

Myoungjoo V Kim

Michael R Bivona

Kang Liu

Eric G Pamer

Ming O Li

Affiliations

Soon will be listed here.

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.

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