(S)-(-)-N-[2-(3-Hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide enhanced the efficacy of anti-PD1 against osteosarcoma cancer

Publication date: Available online 7 November 2018Source: Journal of Bone OncologyAuthor(s): Daokui Qu, Hongbing Wang, Qiuling Bi, Jiangli Xiu, Zhen Liu, Chunsheng WangAbstractImmunotherapies have demonstrated durable clinical responses in various cancers through disinhibiting the immune system, especially for the emergence of anti-programmed cell death protein 1/anti-programmed death-ligand 1 (anti-PD1/anti-PD-L1). However, multiple mechanisms of immune suppression exist in tumors. The recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment is one significant barrier to efficacy of anti-PD1 treatment. MDSCs are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. Here we demonstrate functional inhibition of G-MDSC with (S)-(-)-N-[2-(3-Hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (EA), an inhibitor of PI3Kδ/γ, could prime tumor immune microenvironment and promoted cytotoxic T cell-mediated tumor regression, resultantly enhancing the efficacy of anti-PD1 treatment in a syngeneic osteosarcoma tumor model. EA treatment inhibited G-MDSC function in the tumor tissue. Additionally, combination treatment with EA and anti-PD1 induced CD8+ T lymphocyte-dependent tumor growth delay in osteosarcoma cancer. Our results provided the potential opportunities for new combination strategies to inhibit the function of MDSCs to enhance responses to immune checkpoint blockad...
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research