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Article

A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells

by
Jusong Kim
1,†,
Haeyeon Jang
1,2,†,
Gyu Jin Lee
1,2,†,
Yelim Hur
1,2,
Juhee Keum
1,2,
Jung Ki Jo
3,
Si-Eun Yun
4,
Sung Jun Park
4,
Young Jun Park
4,
Myeong Jun Choi
4,
Kye-Seong Kim
5,6 and
Jaesang Kim
1,2,*
1
Department of Life Science, Ewha Womans University, Seoul 03760, Korea
2
Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 03760, Korea
3
Department of Urology, College of Medicine, Hanyang University, Seoul 04763, Korea
4
R&D Center, Axceso Biopharma Co., Ltd., Yongin 14056, Korea
5
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea
6
Hanyang Biomedical Research Institute, College of Medicine, Hanyang University, Seoul 04763, Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2022, 11(1), 19; https://doi.org/10.3390/cells11010019
Submission received: 11 November 2021 / Revised: 14 December 2021 / Accepted: 17 December 2021 / Published: 22 December 2021
(This article belongs to the Section Cell Signaling)
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Abstract

In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-γ (IFN-γ) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-γ treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-γ-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-γ-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.
Keywords: AX-0085; PD-L1; immune checkpoint; cancer immunotherapy; lung adenocarcinoma AX-0085; PD-L1; immune checkpoint; cancer immunotherapy; lung adenocarcinoma

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MDPI and ACS Style

Kim, J.; Jang, H.; Lee, G.J.; Hur, Y.; Keum, J.; Jo, J.K.; Yun, S.-E.; Park, S.J.; Park, Y.J.; Choi, M.J.; et al. A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells. Cells 2022, 11, 19. https://doi.org/10.3390/cells11010019

AMA Style

Kim J, Jang H, Lee GJ, Hur Y, Keum J, Jo JK, Yun S-E, Park SJ, Park YJ, Choi MJ, et al. A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells. Cells. 2022; 11(1):19. https://doi.org/10.3390/cells11010019

Chicago/Turabian Style

Kim, Jusong, Haeyeon Jang, Gyu Jin Lee, Yelim Hur, Juhee Keum, Jung Ki Jo, Si-Eun Yun, Sung Jun Park, Young Jun Park, Myeong Jun Choi, and et al. 2022. "A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells" Cells 11, no. 1: 19. https://doi.org/10.3390/cells11010019

APA Style

Kim, J., Jang, H., Lee, G. J., Hur, Y., Keum, J., Jo, J. K., Yun, S.-E., Park, S. J., Park, Y. J., Choi, M. J., Kim, K.-S., & Kim, J. (2022). A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells. Cells, 11(1), 19. https://doi.org/10.3390/cells11010019

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