MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer.

ABSTRACT: The immune checkpoint ligand PD-L1 and the transmembrane mucin MUC1 are upregulated in triple-negative breast cancer (TNBC), where they contribute to its aggressive pathogenesis. Here, we report that genetic or pharmacological targeting of the oncogenic MUC1 subunit MUC1-C is sufficient to suppress PD-L1 expression in TNBC cells. Mechanistic investigations showed that MUC1-C acted to elevate PD-L1 transcription by recruitment of MYC and NF-κB p65 to the PD-L1 promoter. In an immunocompetent model of TNBC in which Eo771/MUC1-C cells were engrafted into MUC1 transgenic mice, we showed that targeting MUC1-C associated with PD-L1 suppression, increases in tumor-infiltrating CD8⁺ T cells and tumor cell killing. MUC1 expression in TNBCs also correlated inversely with CD8

SUBMITTER: Maeda T 

PROVIDER: S-EPMC5754244 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature