LAUSR

Adenovirus vector carrying REIC gene (Ad-REIC) is currently in clinical evaluation. The anti-cancer effect of Ad-REIC is mainly caused by two ways, cancer specific apoptosis via endoplasmic reticulum stress with an abundant REIC protein and indirect immune effects by the secreted REIC protein. The former had been well studied that gave us general comprehension of its mechanisms, however latter has still not been fully elucidated. To clear this, we have aimed to identify putative receptor(s) to the extracellularly secreted REIC protein, and have fortunately succeeded to identify five candidates. Surprisingly, the identified receptors all worked to bind with PD-L1 and hold it to stabilize on the plasma membrane, and the REIC binding to the receptors induced liberation of PD-L1 from the receptors’ lock, resulting in an accelerated degradation of PD-L1. This novel insight may lead to the elucidation in important part of the REIC-mediated indirect anti-cancer role. Citation Format: Yuma Gohara, Nahoko Tomonobu, Rie Kinoshata, Lena Audebert, Youyi Chen, Ni Luh Gede Yoni Komalasari, Fan Jiang, Chikako Yoshizawa, Hitoshi Murata, Ken-ichi Yamamoto, Masakiyo Sakaguchi. Novel cancer suppressing role of REIC/DKK3 protein through a downregulation of cell surface PD-L1 in breast cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4931.