Specific inhibition of PI3Kδ/γ enhances the efficacy of anti-PD1 against osteosarcoma cancer.

ABSTRACT: Impressive responses have been observed in patients with cancer treated with checkpoint inhibitory anti-programmed cell death-1 (PD-1) or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies through disinhibiting the immune system. However, tumors possess complex immunosuppressive tumor microenvironment to present therapeutic obstacles and the response rates to immune checkpoint inhibition remain low. One significant barrier to the efficacy of anti-PD1 treatment is the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor. MDSCs dramatically increased in peripheral blood of patients with osteosarcoma and prohibited both T-cell activation and infiltration. Here we demonstrated functional inhibition of G-MDSCs with (S)-(-)-N-[2-(3-Hydroxy-1H-indol-3-yl

SUBMITTER: Shi X 

PROVIDER: S-EPMC6617297 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature