LRP11 activates β-catenin to induce PD-L1 expression in prostate cancer

Abstract

Prostate cancer (PRAD) is associated with abnormal cholesterol metabolism and low-density lipoprotein (LDL) receptor-related protein (LRP) family is essential for the homeostasis of cholesterol. Immune check points like PD-L1 are vital for tumour cells to evade immune attack. However, the potential cross-talk between these two pathways has not been explored before in PRAD. Insight from the regulation mechanism of PD-L1 in PRAD may help to optimise PD-L1 based immunotherapy. In this study, we investigated a regulation network of LRP11/β-catenin/PD-L1 in PRAD. We showed that the expression of LRP11 and PD-L1 was up-regulated in PRAD compared to paired normal tissues. LRP11 expression was positively correlated to PD-L1 expression in PRAD tissues. Further experiments in two PRAD cell lines with LRP11 over-expression and knockdown showed that LRP11 induced PD-L1 expression through β-catenin signalling. In addition, LRP11 over-expression in PRAD cell line induced immunosuppression of Jurkat cell in in-vitro co-culture system. The effects of LRP11 could be blocked by neutralising LRP11 or PD-L1 antibody. Our results provide evidence for a novel regulation mechanism of PD-L1 expression in PRAD and LRP11 may be a potential therapeutic target in PRAD.