RT Journal Article SR Electronic T1 Verteporfin Inhibits PD-L1 through Autophagy and the STAT1–IRF1–TRIM28 Signaling Axis, Exerting Antitumor Efficacy JF Cancer Immunology Research JO Cancer Immunol Res FD American Association for Cancer Research SP 952 OP 965 DO 10.1158/2326-6066.CIR-19-0159 VO 8 IS 7 A1 Liang, Jiyong A1 Wang, Lulu A1 Wang, Chao A1 Shen, Jianfeng A1 Su, Bojin A1 Marisetty, Anantha L. A1 Fang, Dexing A1 Kassab, Cynthia A1 Jeong, Kang Jin A1 Zhao, Wei A1 Lu, Yiling A1 Jain, Abhinav K. A1 Zhou, Zhicheng A1 Liang, Han A1 Sun, Shao-Cong A1 Lu, Changming A1 Xu, Zhi-Xiang A1 Yu, Qinghua A1 Shao, Shan A1 Chen, XiaoHua A1 Gao, Meng A1 Claret, Francois X. A1 Ding, Zhiyong A1 Chen, Jian A1 Chen, Pingsheng A1 Barton, Michelle C. A1 Peng, Guang A1 Mills, Gordon B. A1 Heimberger, Amy B. YR 2020 UL http://cancerimmunolres.aacrjournals.org/content/8/7/952.abstract AB Programmed cell death 1 ligand 1 (PD-L1) is a key driver of tumor-mediated immune suppression, and targeting it with antibodies can induce therapeutic responses. Given the costs and associated toxicity of PD-L1 blockade, alternative therapeutic strategies are needed. Using reverse-phase protein arrays to assess drugs in use or likely to enter trials, we performed a candidate drug screen for inhibitors of PD-L1 expression and identified verteporfin as a possible small-molecule inhibitor. Verteporfin suppressed basal and IFN-induced PD-L1 expression in vitro and in vivo through Golgi-related autophagy and disruption of the STAT1–IRF1–TRIM28 signaling cascade, but did not affect the proinflammatory CIITA-MHC II cascade. Within the tumor microenvironment, verteporfin inhibited PD-L1 expression, which associated with enhanced T-lymphocyte infiltration. Inhibition of chromatin-associated enzyme PARP1 induced PD-L1 expression in high endothelial venules (HEV) in tumors and, when combined with verteporfin, enhanced therapeutic efficacy. Thus, verteporfin effectively targets PD-L1 through transcriptional and posttranslational mechanisms, representing an alternative therapeutic strategy for targeting PD-L1.