Type I interferon gene expression response to chemotherapy

Neoadjuvant and adjuvant chemotherapies provide survival benefits to breast cancer patients by delaying distant relapses or inducing cure, but the mechanism is not fully clear. Here, we performed a gene expression analysis to demonstrate that estrogen-receptor (ER)-negative murine 4T1 mammary adenocarcinoma cells treated by chemotherapy in vitro activate the IFNß/IFNAR/IRF7 pathway to elicit a T cell-dependent immune response that maintains cancer cells in a dormant state in vivo. 10e6 4T1 tumor cells were plated one day prior treatment. For methotrexate (MTX) selection, cells were treated with the dosage close to IC85 directly added into the culture medium. The MTX-containing medium was replaced at the 2nd and 3rd days post starting and then every 2 to 3 days. The in vitro treatment was then continued for up to 2 weeks until single colonies of surviving cells were visible. The resulting surviving cells were the MTX-resistant ones, that we named MR20 compared to the MTX-sensitive WT untreated cells.