Endocrine context is a critical factor that may modulate immune function in breast cancer and, accordingly, should be considered during immunotherapy regimens. Given the immunosuppressive and tolerogenic activities of the sexual hormone progesterone (Pg) and its roles in promoting breast cancer initiation, we aim to evaluate the effect of the antagonist of the progesterone receptor Mifepristone (MFP) as an endocrine therapy to alter the immune profile and to activate the antitumor immune response. We evaluated the MFP-profiled breast cancer immune landscape in a mouse model of luminal tumours and in human tumour samples derived from the MIPRA clinical trial, where breast cancer patients harbouring HR+ tumours were treated with MFP before surgery. Using RNA-seq and flow cytometry, we interrogated the tumour immune infiltration profile, including several global gene expression signatures associated with T-cell exclusion and Immune Checkpoint Inhibitors (ICI) resistance. We observed that treatment with MFP in luminal breast tumours restrains the progestin-mediated tolerogenic infiltrate composed of Tregs and exhausted CD8 and M2 macrophages. Importantly, in tumours, MFP downregulates the suppressive pathway of IDO and Galectin-9, which in turn contributes to the persistence of a population of CD8 T cells that highly produce granzymes and express low TIM3 and PD-1, exhibiting a reinvigorating phenotype. More importantly, we showed that in both mouse models and human tumours, treatment with MFP reverts transcription programs associated with T cell exclusion and ICI resistance and significantly up-regulates programs associated with PD-1/PD-L1 response. Our work provides additional bases for a new therapeutic modality based on the use of antiprogestin endocrine therapy with MFP toward sensitizing luminal breast tumours to ICI treatment.