Tumor-associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically relevant markers for protumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid–binding protein (A-FABP) in TAM promotes breast cancer progression. Although upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis. Furthermore, the protumor effect of A-FABP was mediated by TAM, in particular, in a subset of TAM with a CD11b þ F4/ 80 þ MHCIILy6C phenotype. A-FABP expression in TAM facilitated protumor IL6/STAT3 signaling through regulation of the NFkB/miR-29b pathway. Collectively, our results suggest A-FABP as a new functional marker for protumor TAM. Significance: These findings identify A-FABP as a functional marker for protumor macrophages, thus offering a new target for tumor immunotherapy.
5. 2018 AACR.
Bibliographical noteFunding Information:
The authors thank the Mayo Clinic Genome Analysis Core for the help with performing microRNA expression array of macrophages and Minnesota Supercomputing Institute for computing resources used for the microarray analysis. This work was supported by NIH R01 grants CA18098601A1 (to B. Li), CA17767901A1 (to B. Li), and AI048850 (to J. Suttles).