fig3

Figure 3. Schematic model of chemotherapy-induced immunological dormancy. Primary breast cancer cells escape immune elimination by inducing the expansion of myeloid derived suppressive cells (MDSC) which also promote tumor growth. Chemotherapy induces a type I IFN response in treated tumor cells, resulting in an autocrine and self-sustained increase of IRF7 expression and activation, which in turn induces expression and secretion of IFN-β. Secreted IFN-β binds to IFNAR and induces signaling in both immune cells and tumor cells. IFNARs signaling in tumor cells activates STAT1/STAT2/IRF9 complex which further induces the expression of IFN-β responsive genes including IRF7 resulting in a sustained autocrine IFN-β expression and secretion. Paracrine activation of IFNARs on immune cells stimulates the expansion of tumor suppressive lymphocytes (e.g., CD4⁺ and CD8⁺ T cells) and prevents the mobilization of MDSCs, resulting in the switch of the immune response from immunosuppressive to anti-tumoral