RANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer.

ABSTRACT: Receptor activator of NF-κB ligand (RANKL) and its receptor RANK, are members of the tumor necrosis factor and receptor superfamilies, respectively. Antibodies targeting RANKL have recently been evaluated in combination with anti-CTLA4 in case reports of human melanoma and mouse models of cancer. However, the efficacy of anti-RANKL in combination with antibodies targeting other immune checkpoint receptors such as PD1 has not been reported. In this study, we demonstrated that blockade of RANKL improves anti-metastatic activity of antibodies targeting PD1/PD-L1 and improves subcutaneous growth suppression in mouse models of melanoma, prostate and colon cancer. Suppression of experimental lung metastasis following combination anti-RANKL with anti-PD1 requires NK cells and IFN-γ, whereas subcu

SUBMITTER: Ahern E 

PROVIDER: S-EPMC5980384 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature