Identification of chemical compounds regulating PD ‐L1 by introducing HiBiT‐tagged cells

AbstractProgrammed death ‐ligand 1 (PD‐L1) is a co‐inhibitory molecule expressed on tumor cells. Immune checkpoint inhibitors focusing on the PD‐L1 mechanism are now being studied for the treatment of various cancer types. However, the regulatory mechanism of PD‐L1 is yet to be fully clarified, and a high‐throug hput system for comparing the abilities of small compounds in regulating PD‐L1 has not yet been established. Therefore, we created a HiBiT‐tagged lung adenocarcinoma cell line, PC9‐KI, for easier and faster detection of changes in PD‐L1 protein expression. Using PC9‐KI cells, we screened 1 ,280 chemical compounds from the Library of Pharmacologically Active Compounds (LOPAC) and identified microtubule polymerization inhibitors and thapsigargin as PD‐L1 upregulators and a p97 inhibitor as a PD‐L1 downregulator.

Source: FEBS Letters - January 9, 2021 Category: Biochemistry Authors: Yutaro Uchida, Takahide Matsushima, Ryota Kurimoto, Tomoki Chiba, Yuki Inutani, Hiroshi Asahara Tags: RESEARCH ARTICLE Source Type: research