Orphan Nuclear Receptor Tlx Regulates The Antitumor Immune Response Through Transcriptional Regulation Of Programmed Death Ligand 1 In Glioma

Abstract High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis and novel treatment are urgently needed to improve patient outcomes. Clinical trials of immunotherapies for glioma including PD1/PD-L1 inhibition have performed but the outcome was not optimistic. In this study, we found that orphan nuclear recepter TLX and PD-L1 were both significantly upregulated in glioma lesions and the expression of TLX and PD-L1 in glioma was positively correlated. Moreover, the expression pattern of TLX also associated with a suppression microenvironment in glioma. Functional study revealed that suppression of TLX inhibited glioma cell growth and immune response, which accompanied with down-regulation of PD-L1. We also characterized that TLX could bind directly to PD-L1 promoter and activate PD-L1 gene transcription. Together, our present study shows, for the first time, that TLX can contribute to glioma immune escape via promoting the expression of PD-L1, targeting the druggable TLX may have a potential therapeutic significance in glioma immune therapy. Citation Format: Jiayi Zhou, Xiaojuan Pei, Zhu Wang, Weijie Gao, Franky Leung Chan, Xin Li, Jie Mao, Dinglan Wu. Orphan nuclear receptor TLX regulates the antitumor immune response through transcriptional regulation of programmed death ligand 1 in glioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1007.