Inhibition of Notch enhances efficacy of immune checkpoint blockade in triple-negative breast cancer.

ABSTRACT: Aberrant Notch, which is a defining feature of triple-negative breast cancer (TNBC) cells, regulates intercellular communication in the tumor immune microenvironment (TIME). This includes tumor-associated macrophage (TAM) recruitment through Notch-dependent cytokine secretion, contributing to an immunosuppressive TIME. Despite the low response rate of TNBC to immune checkpoint blockade (ICB), here, we report that inhibition of Notch-driven cytokine-mediated programs reduces TAMs and induces responsiveness to sequentially delivered ICB. This is characterized by the emergence of GrB⁺ cytotoxic T lymphocytes (CTLs) in the primary tumor. A more impressive effect of sequential treatment is observed in the lung where TAM depletion and increased CTLs are accompanied by near-complete ab

SUBMITTER: Shen Q 

PROVIDER: S-EPMC11524187 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature