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.

中文翻译：

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LRP11 激活 β-catenin 以诱导前列腺癌中的 PD-L1 表达。

前列腺癌 (PRAD) 与胆固醇代谢异常有关，低密度脂蛋白 (LDL) 受体相关蛋白 (LRP) 家族对胆固醇的稳态至关重要。PD-L1 等免疫检查点对于肿瘤细胞逃避免疫攻击至关重要。然而，之前在 PRAD 中尚未探索过这两种途径之间的潜在串扰。洞察 PRAD 中 PD-L1 的调控机制可能有助于优化基于 PD-L1 的免疫疗法。在本研究中，我们研究了 PRAD 中 LRP11/β-catenin/PD-L1 的调控网络。我们发现，与配对的正常组织相比，PRAD 中 LRP11 和 PD-L1 的表达上调。LRP11 表达与 PRAD 组织中的 PD-L1 表达呈正相关。在 LRP11 过表达和敲低的两个 PRAD 细胞系中的进一步实验表明，LRP11 通过 β-连环蛋白信号传导诱导 PD-L1 表达。此外，在体外共培养系统中，PRAD 细胞系中的 LRP11 过表达诱导了 Jurkat 细胞的免疫抑制。LRP11 的作用可以通过中和 LRP11 或 PD-L1 抗体来阻断。我们的结果为 PRAD 中 PD-L1 表达的新调节机制提供了证据，LRP11 可能是 PRAD 的潜在治疗靶点。