Residual disease is a major hurdle in the eradication of human cancer. We have reproduced this by showing that mammary tumors arising in a mouse model for BRCA1-deficient breast cancer are also not easily eradicated by monotherapy with PARP inhibitors or platinum drugs, despite their high sensitivity to these cytotoxic agents. Tumor regrowth appears to originate from slowly cycling cells with a 2n DNA content that did not enter the S/G₂/M phases of the cell cycle during treatment. To identify tumor-intrinsic mechanisms of drug resistance we characterized residual 2n tumor cells by RNAseq in our model. For this purpose, GFP-labelled 2n tumor cells were sorted from residual tumors after cisplatin treatment. We found that these cells display an increased expression of genes encoding immunosuppressive factors including IL-10 and TGF-$\beta $, as well as the negative costimulatory signals of the PD-1/PD-L1 and the CTLA-4/B7 axis. By blocking inhibitory T-cell signaling using antibodies directed against CTLA-4 and PD-1 in combination with cisplatin or PARP inhibitors, we attempted at overcoming the immunosuppressive microenvironment in BRCA1-deficient tumors and eradicate residual tumor cells. Expectedly, the combination of CTLA-4 and PD-1-targeting antibodies with the PARP-inhibitor olaparib led to an increase in CD8-positive cytotoxic T-cells in tumor remnants. Remarkably, this increase did not result in a therapeutic benefit and we were not able to eradicate the drug-tolerant tumor cells in vivo using this combination immunotherapy approach. This outcome might be due to other redundant immunosuppressive factors expressed by residual tumor cells as indicated by the increased number of tumor-infiltrating FoxP3-positive T-regulatory cells. Such adverse activation of T-regulatory cells upon immunotherapy may be relevant for the clinic and could explain some of the cases in which CTLA-4 and PD-1-blocking immunotherapy failed.