CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer.

ABSTRACT: Tumor-associated myeloid cells regulate tumor growth and metastasis, and their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase kinase (CaMKK2) to be highly expressed within intratumoral myeloid cells in mouse models of breast cancer, and demonstrate that its inhibition within myeloid cells suppresses tumor growth by increasing intratumoral accumulation of effector CD8⁺ T cells and immune-stimulatory myeloid subsets. Tumor-associated macrophages (TAMs) isolated from Camkk2^-/- mice expressed higher levels of chemokines involved in the recruitment of effector T cells compared to WT. Similarly, in vitro generated Camkk2^-/- macrophages recruit more T cells, and have a reduced capability to suppress

SUBMITTER: Racioppi L 

PROVIDER: S-EPMC6547743 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature