CD4 cells re-educate tumor associated macrophages.. Mus musculus

Tumor Associated Macrophages (TAMs) are known to release cytokines/chemokines that promote tumor survival and angiogenesis. Little is known, however, about their ability to present tumor antigens to CD4 T cells, nor whether such presentation might switch their tumor supporting function. Here we show that TAMs present tumor antigens to CD4 T cells and that upon antigen recognition, the T cells re-educate the TAMs to produce lower amounts of tumor nurturing proteins and greater amounts of anti-angiogenic proteins. The CD4-educated-TAMs display a gene signature characterized by upregulation of INFgamma esponsive genes that have anti-viral and anti-bacterial function. This phenotypic switch is INF-gamma dependent, and necessary for CD4-mediated tumor rejection. CD4-based immunotherapies could take advantage of this re-education process to improve cancer treatment. Overall design: The experiment consisted of six untreated Tumor Associated Macrophages (TAMs) and six CD4-treated Tumor Associated Macrophages (TAMs) for a total of 12 samples. For each of the treated and untreated samples, two were technical replicates and four were biological replicates.