Abstract 1555: Nuclear accumulation of cell surface programmed cell death ligand 1 promotes metastatic outgrowth in triple-negative breast cancer cells

Abstract PD-L1 presented on the cancer cell surface is well known for its role in immune checkpoint regulation by interacting with PD-1 on immune cells. On the other hand, it has been reported that PD-L1 is localized in the cancer cells’ nuclei, where the nuclear PD-L1 (nPD-L1) is conducive to cancer outgrowth and motility. However, there has yet to be reported about the mechanistic insight into the event. In this study, we, therefore, aimed to clarify still unidentified points in the nPD-L1-mediated event. Our efforts revealed that the upregulation is induced by a functional suppression of nuclear protein X (tentative name), which we identified as a novel binding protein with nPD-L1 at its cytoplasmic tail. Their nuclear interaction also abolished an aggressive cancer proclivity, epithelial-mesenchymal transition (EMT). The mechanism is helpful to the complex nature of PD-L1 in plural cancer cell behaviors. Citation Format: Yuma Gohara, Nahoko Tomonobu, Rie Kinoshita, Kenichi Yamamoto, Hitoshi Murata, Masakiyo Sakaguchi. Nuclear accumulation of cell surface programmed cell death ligand 1 promotes metastatic outgrowth in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1555.