Soluble PD-L1 works as a decoy in lung cancer immunotherapy via alternative polyadenylation

• DOI: 10.1172/jci.insight.153323
• Publication Date: 2021-12-07T17:01:21Z
• Authors: Ray Sagawa; Seiji Sakata; Bo Gong; Yosuke Seto; Ai Takemoto; Satoshi Takagi; Hironori Ninomiya; Noriko Yanagitani; Masayuki Nakao; Mingyon Mun; Ken Uchibori; Makoto Nishio; Yasunari Miyazaki; Yuichi Shiraishi; Seishi Ogawa; Keisuke Kataoka; Naoya Fujita; Kengo Takeuchi; Ryohei Katayama
• Keywords: Decoy; Immune checkpoint; Cancer Immunotherapy

Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer and has been applied to clinical medicine. However, there are still some problems, including relatively low response rate, innate mechanisms of resistance against immune blockades, absence reliable biomarkers predict responsiveness. In this study vitro vivo models, we demonstrate that PD-L1-vInt4, splicing variant PD-L1, plays role as decoy anti-PD-L1 antibody treatment. First, showed PD-L1-vInt4 was detectable samples it possible visualize secreting variants with IHC. By overexpressing PD-L1-secreted on MC38 cells, observed an immune-suppressing effect not induced by their secretion alone. We then demonstrated resisted treatment, compared WT which explicable PD-L1-vInt4's decoying antibody. The function PD-L1 may be one reasons for cancers being resistant therapy. Measuring serum levels might helpful deciding therapeutic strategy.