HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment.
CG-745
Colorectal cancer
HDAC
Hepatocellular carcinoma
MDSC
PD-1
TME
Treg
Journal
Journal of Cancer
ISSN: 1837-9664
Titre abrégé: J Cancer
Pays: Australia
ID NLM: 101535920
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
02
2020
accepted:
11
03
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
6
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32368288
doi: 10.7150/jca.44622
pii: jcav11p4059
pmc: PMC7196255
doi:
Types de publication
Journal Article
Langues
eng
Pagination
4059-4072Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
Références
Exp Mol Med. 2018 Dec 13;50(12):1-11
pubmed: 30546008
Clin Cancer Res. 2017 Sep 1;23(17):5187-5201
pubmed: 28698201
J Immunol Methods. 2001 Jan 1;247(1-2):1-8
pubmed: 11150531
Mol Ther Oncolytics. 2019 Mar 19;13:1-6
pubmed: 30976658
Science. 2009 Aug 14;325(5942):834-40
pubmed: 19608861
Oncotarget. 2017 Jul 4;8(27):44159-44170
pubmed: 28498806
Onco Targets Ther. 2018 Oct 04;11:6505-6524
pubmed: 30323625
Nat Rev Immunol. 2018 Oct;18(10):617-634
pubmed: 30022149
Invest New Drugs. 2012 Aug;30(4):1434-42
pubmed: 21773733
Clin Epigenetics. 2012 Mar 12;4(1):5
pubmed: 22414492
J Cell Sci. 2012 Dec 1;125(Pt 23):5591-6
pubmed: 23420197
Front Immunol. 2019 Mar 19;10:453
pubmed: 30941125
Trends Cell Biol. 2019 Oct;29(10):777-790
pubmed: 31378317
Nat Commun. 2015 Apr 27;6:6838
pubmed: 25913720
Cell Rep. 2015 Nov 17;13(7):1444-1455
pubmed: 26549458
Expert Rev Anticancer Ther. 2010 Jun;10(6):935-54
pubmed: 20553216
Chonnam Med J. 2016 Jan;52(1):1-11
pubmed: 26865995
J Immunol. 2010 Sep 15;185(6):3489-97
pubmed: 20702731
PLoS One. 2015 Mar 17;10(3):e0119379
pubmed: 25781604
Genes Dev. 1998 Mar 1;12(5):599-606
pubmed: 9499396
Trends Immunol. 2011 Jul;32(7):335-43
pubmed: 21570914
Clin Epigenetics. 2019 Jan 17;11(1):11
pubmed: 30654849
J Immunol. 2010 May 1;184(9):4631-6
pubmed: 20308634
J Leukoc Biol. 2010 Jun;87(6):1103-14
pubmed: 20200406
Ann Transl Med. 2015 Oct;3(18):267
pubmed: 26605313
Ann Oncol. 2016 Aug;27(8):1482-92
pubmed: 27069014
Sci Rep. 2019 Feb 20;9(1):2350
pubmed: 30787420
Cancer Immunol Res. 2018 Dec;6(12):1561-1577
pubmed: 30341213
Cancer Discov. 2018 Sep;8(9):1069-1086
pubmed: 30115704
ISRN Hematol. 2012;2012:690901
pubmed: 22461998
Blood. 2011 Jan 27;117(4):1102-3
pubmed: 21273326
Sci Rep. 2017 Jan 30;7:41615
pubmed: 28134290
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Nat Rev Clin Oncol. 2018 Feb;15(2):81-94
pubmed: 29115304
Mol Ther. 2013 Apr;21(4):887-94
pubmed: 23295947
Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15782-7
pubmed: 17043231
Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2404-9
pubmed: 16141407
Antimicrob Agents Chemother. 2015 Dec 28;60(3):1521-9
pubmed: 26711769
BMC Cancer. 2016 Sep 30;16(1):763
pubmed: 27716272
J Clin Invest. 2007 May;117(5):1137-46
pubmed: 17476343
Cancer Immunol Res. 2019 Aug;7(8):1318-1331
pubmed: 31235619
Oncotarget. 2017 May 17;8(47):83155-83170
pubmed: 29137331
Sci Rep. 2017 Sep 7;7(1):10921
pubmed: 28883618
Exp Mol Med. 2019 Aug 26;51(8):1-15
pubmed: 31451695