Immunological barriers to immunotherapy in primary and metastatic breast cancer

Patients with breast cancer obtain limited clinical benefits from immune checkpoint inhibitors (ICIs), pointing to the existence of multiple immunological alterations that cannot be simultaneously normalized with immunotherapy. Accumulating preclinical evidence suggests that radiation therapy (RT) can be harnessed to sensitize primary and metastatic mouse mammary carcinomas to ICIs. However, various clinical trials combining RT with ICIs in patients with breast cancer documented little cooperativity. Here, we discuss immunological barriers that may prevent RT from unlocking the therapeutic potential of ICIs in patients with breast cancer. These observations may inspire the development of combinatorial regimens that might benefit patients with diverse neoplastic conditions including brain tumors.