Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors.

Two experiments have been performed at the Accelerator Laboratory of the Department of Physics, University of Jyväskylä, Finland, and are reported here. The first experiment was a recoil-decay tagging study intended to delineate the level scheme of 226U for the first time. The subsequent experiment, the observation of fine structure in the a decay of 230Pu, was to obtain an improved measurement of the excitation energy of the first excited 2+ state, which was tentatively assigned in the first experiment.