Depletion of plasmacytoid dendritic cells inhibits tumor growth and prevents bone metastasis of breast cancer cells.

ABSTRACT: Elevated levels of plasmacytoid dendritic cells (pDC) have been reported in breast cancer patients, but the significance remains undefined. Using three immunocompetent mouse models of breast cancer bone metastasis, we identified a key role for pDC in facilitating tumor growth through immunosuppression and aggressive osteolysis. Following infiltration of macrophages upon breast cancer dissemination, there was a steady increase in pDC within the bone, which resulted in a sustained Th2 response along with elevated levels of regulatory T cells and myeloid-derived suppressor cells. Subsequently, pDC and CD4(+) T cells, producing osteolytic cytokines, increased with tumor burden, causing severe bone damage. Microcomputed tomography and histology analyses of bone showed destruction of femur and t

SUBMITTER: Sawant A 

PROVIDER: S-EPMC3531993 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature