J Cancer
2020; 11(14):4059-4072.
doi:10.7150/jca.44622 This issueCite
Research Paper
HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment
Young-Dae Kim*, Sang-Min Park*, Hae Chan Ha, A Reum Lee, Heeyoung Won, Hyunju Cha, Sangsook Cho, Joong Myung Cho✉
Institute for Drug Discovery, CrystalGenomics, Inc., Korea Bio Park, 700 Daewangpangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea *These authors provided equal contribution
Kim YD, Park SM, Ha HC, Lee AR, Won H, Cha H, Cho S, Cho JM. HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment. J Cancer 2020; 11(14):4059-4072. doi:10.7150/jca.44622. https://www.jcancer.org/v11p4059.htm
Histone deacetylase inhibitors (HDACis) are well-known epigenetic regulators with therapeutic potential in various diseases. Recent studies have shown that HDACis are involved in immune-mediated anti-cancer effects and may modulate the activity of immunotherapy agents. CG-745, a histone deacetylase inhibitor, has shown anti-cancer effects in pancreatic cancer, colorectal cancer, and non-small cell lung cancer. However, the exact role of CG-745 within the immune system is largely unknown. In this study, we have shown that CG-745 induces microenvironment changes promoting anti-cancer effect of anti-PD-1 antibody in syngeneic mouse models. Specifically, CG-745 induces or extends IL-2 and IFN-γ expression with or without additional stimulation, and increases proliferation of cytotoxic T cells and NK cells, while inhibiting proliferation of regulatory T cells. The analysis of immune cell distribution in the tumor microenvironment and spleen reveals that CG-745 suppresses M2 macrophage polarization and decreases the myeloid-derived suppressor cells. Recent advances in immunotherapy highlight the anti-cancer effects of immune checkpoint inhibitor despite a relatively limited clinical benefit in the subset of patients. Our results indicate that CG-745 enables the synergistic effects of the immune checkpoint inhibitor combination therapy in various cancers by suppressing tumor microenvironment.
Kim, Y.D., Park, S.M., Ha, H.C., Lee, A.R., Won, H., Cha, H., Cho, S., Cho, J.M. (2020). HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment. Journal of Cancer, 11(14), 4059-4072. https://doi.org/10.7150/jca.44622.
ACS
Kim, Y.D.; Park, S.M.; Ha, H.C.; Lee, A.R.; Won, H.; Cha, H.; Cho, S.; Cho, J.M. HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment. J. Cancer 2020, 11 (14), 4059-4072. DOI: 10.7150/jca.44622.
NLM
Kim YD, Park SM, Ha HC, Lee AR, Won H, Cha H, Cho S, Cho JM. HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment. J Cancer 2020; 11(14):4059-4072. doi:10.7150/jca.44622. https://www.jcancer.org/v11p4059.htm
CSE
Kim YD, Park SM, Ha HC, Lee AR, Won H, Cha H, Cho S, Cho JM. 2020. HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment. J Cancer. 11(14):4059-4072.
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