Estrogen receptor signaling drives immune evasion and immunotherapy resistance in HR+ breast cancer.

ABSTRACT: Hormone receptor-positive (HR+) breast cancers (BCs) are typically "immune-cold," poorly immune-infiltrated tumors that do not respond to immune-checkpoint blockade (ICB) therapies. Using clinical data, we report that estrogen receptor α (ERα) signaling was associated with immunosuppressive pathways and a lack of response to ICB in patients with HR+ BC. In this study, we validated ER-mediated immunosuppression by engineering and modulating the ER in preclinical models in vitro, in vivo, and ex vivo. Mechanistically, we found that ERα hijacked LCOR, a nuclear receptor corepressor, thereby preventing LCOR's function in the induction of tumor immunogenicity and immune infiltration, which is normally observed in the absence of ERα, such as in ER- BC. In HR+ BC, we demonstrate that the molecula

SUBMITTER: Palomeque JA 

PROVIDER: S-EPMC12807476 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature