CD276 (also known as B7–H3, an immune checkpoint molecule) is aberrantly overexpressed in many cancers. However, the upregulation mechanism and in particular, whether oncogenic signaling has a role, is unclear. Here we demonstrate that a pro-oncogenic kinase PBK, the expression of which is associated with immune infiltration in nasopharyngeal carcinoma (NPC), stimulates the expression of CD276 epigenetically. Mechanistically, PBK phosphorylates MSL1 and enhances the interaction between MSL1 and MSL2, MSL3, and KAT8, the components of the MSL complex. As a consequence, PBK promotes the enrichment of MSL complex on CD276 promoter, leading to the increased histone H4 K16 acetylation and the activation of CD276 transcription. In addition, we show that CD276 is highly upregulated and associated with immune infiltrating levels in NPC. Collectively, our findings describe a novel PBK/MSL1/CD276 signaling axis, which may play an important role in immune evasion of NPC and may be targeted for cancer immunotherapy.

CD276（也称为 B7-H3，一种免疫检查点分子）在许多癌症中异常过度表达。然而，上调机制，特别是致癌信号传导是否发挥作用尚不清楚。在这里，我们证明了一种促癌激酶 PBK，其表达与鼻咽癌 (NPC) 的免疫浸润相关，可在表观遗传学上刺激CD276的表达。从机制上讲，PBK 磷酸化 MSL1 并增强 MSL1 与 MSL2、MSL3 和 KAT8（MSL 复合物的组成部分）之间的相互作用。因此，PBK 促进 MSL 复合物在CD276启动子上富集，导致组蛋白 H4 K16 乙酰化增加并激活CD276转录。此外，我们发现CD276高度上调并与鼻咽癌中的免疫浸润水平相关。总的来说，我们的研究结果描述了一种新的 PBK/MSL1/CD276 信号轴，它可能在 NPC 的免疫逃避中发挥重要作用，并可能成为癌症免疫治疗的目标。