Abstract 1534: CD163-expressing macrophages constitute a distinct malignancy-promoting phenotype in melanoma facilitating tumor development, progression, and metastasis: Implications for novel anticancer therapy.

Abstract

Abstract Tumor-infiltrating macrophages are recruited to the tumor microenvironment and believed to play a key role in tumor development, progression, and metastasis by producing growth factors and promoting neoangiogenesis. Here, we show that CD163-expressing macrophages express a distinct gene expression signature capable of facilitating tumor development and progression. This supports our earlier findings showing significant correlation between CD163+ macrophage density, tumor grade, and poor prognosis in patients with melanoma. Selective eradication of CD163-expressing tumor-associated macrophages through receptor-mediated delivery of nanoparticles encapsulating the cytotoxic agent doxorubicin significantly inhibited tumor formation and prolonged survival in an immune-competent conditional mouse model of BrafV600E-induced, Pten-deficient metastatic melanoma. High-resolution dynamic intravital imaging showed specific targeting of a subpopulation of tumor-infiltrating macrophages expressing the scavenger receptor CD163, including Tie2-expressing macrophages recently identified as being highly proangiogenic. In conclusion, our findings identify CD163-expressing macrophages as a distinct malignancy-promoting phenotype and indicate a novel therapeutic target in cancer. Citation Format: Maciej B. Maniecki, Anders Etzerodt, William E. Damsky Jr., Aisha Rafique, David Gonzalez, Lars Dyrskjøt, Holger J. Møller, Marcus W. Bosenberg, Søren K. Moestrup. CD163-expressing macrophages constitute a distinct malignancy-promoting phenotype in melanoma facilitating tumor development, progression, and metastasis: Implications for novel anticancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1534. doi:10.1158/1538-7445.AM2013-1534