Chemotherapy induces enrichment of CD47 ⁺ /CD73 ⁺ /PDL1 ⁺ immune evasive triple-negative breast cancer cells

Significance Cytotoxic chemotherapy is frequently used in patients with triple-negative breast cancer (TNBC). Although patients initially respond to the treatment, the cancer often comes back and kills the patient. Recent studies have demonstrated that cancer cells express genes that protect them from killing by immune cells, but the stimulus that prompts this response is unknown. We show that when TNBC cells are treated with chemotherapy, the surviving cells turn on genes that enable them to escape killing by the immune system. We identify hypoxia-inducible factors (HIFs), which are known to promote metastasis of TNBC, as responsible for this countertherapeutic effect. We show that coadministration of an HIF inhibitor with chemotherapy blocks the ability of surviving TNBC cells to evade the immune system.