A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-gamma-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells
- 주제(키워드) AX-0085 , PD-L1 , immune checkpoint , cancer immunotherapy , lung adenocarcinoma
- 주제(기타) Cell Biology
- 설명문(일반) [Kim, Jusong; Jang, Haeyeon; Lee, Gyu Jin; Hur, Yelim; Keum, Juhee; Kim, Jaesang] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Jang, Haeyeon; Lee, Gyu Jin; Hur, Yelim; Keum, Juhee; Kim, Jaesang] Ewha Womans Univ, Ewha Res Ctr Syst Biol, Seoul 03760, South Korea; [Jo, Jung Ki] Hanyang Univ, Coll Med, Dept Urol, Seoul 03760, South Korea; [Yun, Si-Eun; Park, Sung Jun; Park, Young Jun; Choi, Myeong Jun] Axceso Biopharma Co Ltd, R&D Ctr, Yongin 14056, South Korea; [Kim, Kye-Seong] Hanyang Univ, Grad Sch Biomed Sci & Engn, Seoul 04763, South Korea; [Kim, Kye-Seong] Hanyang Univ, Hanyang Biomed Res Inst, Coll Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190321
- 본문언어 영어
- Published As https://doi.org/10.3390/cells11010019
- PubMed https://pubmed.ncbi.nlm.nih.gov/35011581
초록/요약
In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-gamma (IFN-gamma) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-gamma treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-gamma-mediated repression of T cell activation in vitro and enhances the anti-tumor activity of anti-PD-1 antibody in vivo when used in combination. Finally, transcriptomic analyses indicated that AX-0085 is highly specific in targeting the IFN-gamma-pathway, thereby raising the possibility of applying this reagent in combination therapy with checkpoint inhibitor antibodies. It may be particularly relevant in cases in which PD-L1-mediated T cell exhaustion leads to immunoevasive phenotypes.
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