Although the immune checkpoint function of PD-L1 has dominated its study, we report that PD-L1 has an unanticipated intrinsic function in promoting the dynamics of persistent cell migration. PD-L1 concentrates at the rear of migrating carcinoma cells where it facilitates retraction, resulting in the formation of PD-L1–containing retraction fibers and migrasomes. PD-L1 promotes retraction by interacting with and localizing the β4 integrin to the rear enabling this integrin to stimulate contractility. This mechanism involves the ability of PD-L1 to maintain cell polarity and lower membrane tension at the cell rear compared with the leading edge that promotes the localized interaction of PD-L1 and the β4 integrin. This interaction enables the β4 integrin to engage the actin cytoskeleton and promote RhoA-mediated contractility. The implications of these findings with respect to cell-autonomous functions of PD-L1 and cancer biology are significant.

中文翻译：

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PD-LI 通过改变整合素 β4 动力学促进持续细胞迁移过程中的后缩


尽管 PD-L1 的免疫检查点功能主导了其研究，但我们报告称 PD-L1 在促进持续细胞迁移的动态方面具有意想不到的内在功能。 PD-L1 集中在迁移癌细胞的后部，促进癌细胞回缩，从而形成含有 PD-L1 的回缩纤维和迁移体。 PD-L1 通过与 β4 整合素相互作用并将其定位到后方来促进收缩，从而使该整合素能够刺激收缩性。该机制涉及 PD-L1 维持细胞极性和降低细胞后部膜张力（与前缘相比）的能力，从而促进 PD-L1 和 β4 整联蛋白的局部相互作用。这种相互作用使 β4 整合素能够与肌动蛋白细胞骨架结合并促进 RhoA 介导的收缩性。这些发现对于 PD-L1 的细胞自主功能和癌症生物学具有重要意义。