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Identification of chemical compounds regulating PD‐L1 by introducing HiBiT‐tagged cells
Author(s) -
Uchida Yutaro,
Matsushima Takahide,
Kurimoto Ryota,
Chiba Tomoki,
Inutani Yuki,
Asahara Hiroshi
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14032
Subject(s) - chemistry , pd l1 , cancer research , microbiology and biotechnology , cancer cell , schizosaccharomyces pombe , immune system , cancer , biochemistry , biology , saccharomyces cerevisiae , immunotherapy , yeast , genetics
Programmed 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‐throughput 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 1280 chemical compounds from the Library of Pharmacologically Active Compounds and identified microtubule polymerization inhibitors and thapsigargin as PD‐L1 upregulators and a p97 inhibitor as a PD‐L1 downregulator.