MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor immune microenvironment in triple-negative breast cancer

Immune checkpoint inhibitors (ICIs) have had a profound impact on the treatment of many tumors; however, their effectiveness against triple-negative breast cancers (TNBCs) has been limited. One factor limiting responsiveness of TNBCs to ICIs is a lack of functional tumor i-infiltrating lymphocytes (TILs) in ‘“non-inflamed’” or ‘“cold’” tumor immune microenvironments (TIMEs), albeitalthough by unknown mechanisms. Targeting MUC1-C in a mouse transgenic TNBC tumor model increases cytotoxic tumor -infiltrating CD8 + T cells (CTLs), supporting a role for MUC1-C in immune evasion. The basis for these findings and whether they extend to human TNBCs are not known. Human TNBC cells (BT-549) silenced for MUC1-C using doxycycline inducible shRNAs were analyzed for the effects of MUC1-C on global transcriptional profiles.