The Macrophage Migration Inhibitory Factor (MIF) is an inflammatory cytokine that has been well-characterized as a mediator of numerous inflammatory disease processes. We have previously demonstrated that expression of MIF in the primary tumor promotes growth and metastasis in the 4T1 murine model of breast cancer. MIF is overexpressed in many cancer types, including breast cancer, and the degree of MIF expression correlates with tumor aggressiveness. We therefore sought to understand the link between primary tumor expression of MIF and increased tumor growth and metastasis. As a cytokine, we hypothesized that MIF would function by controlling some aspect of the interaction between tumor and host immune system. This was supported by our observation that MIF expression was no longer required for growth and metastasis in an immunodeficient SCID/bg host. Using flow cytometry, we discovered that MIF expression in the primary tumor decreased the abundance of intra-tumoral CD8+ T cells, as well as inhibited those cells' ability to produce the cytokine IFNgamma. We also found that depletion of T cells from MIF KD tumor bearing mice restored tumor growth to the level of WT tumors, while this depletion had no effect on the growth of WT tumors. This suggests that T cells are playing an important role in the control of tumor growth seen in MIF KD tumors. Previous work in the lab has also shown that MIF expression in the primary tumor increased the abundance of an immunosuppressive cell subset known as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We hypothesize that this population of cells is responsible for the reduced T cell infiltration and activity seen MIF-expressing tumors, and we aim to determine the mechanisms by which MIF promotes MDSC accumulation and/or function, and how the MDSCs are inhibiting T cell activity in the tumor.

Citation Format: Kristen N. Balogh, Janet V. Cross. A role for Macrophage Migration Inhibitory Factor (MIF) in breast cancer growth and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A03.