Abstract 2791: RelB upregulates PD-L1 in advanced prostate cancer: An insight into tumor immunoescape

Abstract

Abstract Interaction between programmed death (PD)-1 receptor and its ligand (PD-L1) is essential for suppression of activated T-lymphocytes. Thus, the high level of PD-L1 in tumors is critical for triggering the inhibitory effect on T cell responses leading to immunoescape. However, the mechanism underlying PD-L1 overexpression in cancers remains fully elucidated. Hence, we demonstrate that PD-L1 is uniquely expressed at a high level in advanced prostate cancer with high constitutive RelB, a member to drive the NF-κB alternative pathway. Clinical investigation indicated that the high levels of RelB/PD-L1 are correlated to the patient’s Gleason scores, which was confirmed by quantification of their levels in several prostate cancer cell lines vs. normal prostate epithelial cell. Knocked out RelB in androgen-independent PC-3 cells resulted in reducing PD-L1 expression. Consistently, ectopic expression of RelB in androgen-dependent 22Rv1 cells led to increasing PD-L1 level, implicating that RelB participates in PD-L1 regulation in prostate cancer. Cytokine IFN-γ is able to induce PD-L1 expression through promoting RelB nuclear translocation, revealing that RelB may directly regulate PD-L1 transcription. Accordingly, an NF-κB enhancer element was identified in the promoter region, which is responsible for RelB-mediated PD-L1 transcriptional activation. These results suggest that overexpression of PD-L1 in advanced prostate cancer is, at least in part, through RelB activation. The finding from this study provides a potential approach for enhancing immunotherapeutic efficiency by targeting RelB-activated NF-κB alternative pathway. Note: This abstract was not presented at the meeting. Citation Format: Yanyan Zhang, Shuyi Zhu, Peipei Qian, Xiumei Wang, Zhi Xu, Wenbo Sun, Yong Xu. RelB upregulates PD-L1 in advanced prostate cancer: An insight into tumor immunoescape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2791.