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Tackling tumor-associated macrophages beats breast and other cancers in mice Tumor-associated macrophages (TAMs) can promote the growth and spread of tumor cells. In a study appearing online on July 20 in advance of print publication in the August issue of the Journal of Clinical Investigation, Rong Xiang and colleagues from The Scripps Research Institute have designed a cancer vaccine to specifically target these cells. In this study, TAMs but not tumor cells or other macrophage populations, were found to express high levels of the enzyme legumain, so the authors generated a DNA vaccine encoding legumain. When administered to mice, this vaccine inhibited tumor growth and spread in mouse models of breast, colon, and non–small cell lung cancer. These effects appeared to result from legumain-specific CD8+ T cells targeting TAMs around the tumor for killing. Consistent with the marked decrease in the number of TAMs in the tumor tissue of vaccinated mice, tumors contained decreased amounts of the tumor cell growth factor TNF and the growth factor VEGF, which resulted in reduced tumor cell spread and limited the growth of new blood vessels to the tumor. The authors suggest that this demonstration that targeting TAMs can suppress tumor growth and metastasis could lead to the development of new therapies for cancer. TITLE: Targeting tumor-associated macrophages as a novel strategy against breast cancer AUTHOR CONTACT: Rong Xiang The Scripps Research Institute, La Jolla, California, USA. E-mail: rxiang@scripps.edu. View the PDF of this article at: http://https://www.the-jci.org/article.php?id=27648 ### JCI table of contents: July 20, 2006
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