Abstract SY40-04: Immune control of spontaneous tumor development

Abstract

Abstract Long recognized as an evolutionarily ancient cell type to control development, tissue homeostasis, and immune responses to pathogens, macrophages are being rediscovered as regulators of several chronic disorders including cancer. Using a spontaneous mammary tumor model, here we show that tumor growth induces the differentiation and expansion of a unique subset of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). Compared to MTMs, TAMs do not exhibit an “alternatively activated macrophage” phenotype, but express the adhesion molecule Vcam1, and have high proliferative capacity upon their differentiation from CCR2-expressing inflammatory monocytes. Importantly, TAM differentiation is dependent on the transcriptional regulator of the Notch signaling pathway, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses, and suppresses tumor growth. These findings demonstrate that TAMs represent a novel lineage of mononuclear phagocytes with critical regulatory functions in promoting T cell tolerance to tumors. Citation Format: Ming Li. Immune control of spontaneous tumor development. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr SY40-04. doi:10.1158/1538-7445.AM2014-SY40-04