Programmed death ligand-1 (PD-L1 or B7-H1) is well known for its role in immune checkpoint regulation, but its function inside the tumor cells has rarely been explored. Here we report that nuclear PD-L1 is important for cancer cell sister chromatid cohesion. We found that depletion of PD-L1 suppresses cancer cell proliferation, colony formation in vitro, and tumor growth in vivo in immune-deficient NSG mice independent of its role in immune checkpoint. Specifically, PD-L1 functions as a subunit of the cohesin complex, and its deficiency leads to formation of multinucleated cells and causes a defect in sister chromatid cohesion. Mechanistically, PD-L1 compensates for the loss of Sororin, whose expression is suppressed in cancer cells overexpressing PD-L1. PD-L1 competes with Wing Apart-Like (WAPL) for binding to PDS5B, and secures proper sister chromatid cohesion and segregation. Our findings suggest an important role for nuclear PD-L1 in cancer cells independent of its function in immune checkpoint.

中文翻译：

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核 PD-L1 对姐妹染色单体凝聚力的调节。


程序性死亡配体-1（PD-L1 或 B7-H1）以其在免疫检查点调节中的作用而闻名，但其在肿瘤细胞内的功能却很少被探索。在这里，我们报告核 PD-L1 对于癌细胞姐妹染色单体的凝聚力很重要。我们发现，PD-L1 的缺失会抑制免疫缺陷 NSG 小鼠体内的癌细胞增殖、体外集落形成和体内肿瘤生长，而与其在免疫检查点中的作用无关。具体来说，PD-L1 作为粘连蛋白复合物的一个亚基发挥作用，其缺陷会导致多核细胞的形成并导致姐妹染色单体粘连缺陷。从机制上讲，PD-L1 可以补偿 Sororin 的损失，而索罗林的表达在过度表达 PD-L1 的癌细胞中受到抑制。 PD-L1 与 Wing Apart-Like (WAPL) 竞争与 PDS5B 的结合，并确保适当的姐妹染色单体凝聚和分离。我们的研究结果表明核 PD-L1 在癌细胞中的重要作用与其在免疫检查点中的功能无关。