Back to Search
Start Over
TMP195 Exerts Antitumor Effects on Colorectal Cancer by Promoting M1 Macrophages Polarization.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2022 Sep 06; Vol. 18 (15), pp. 5653-5666. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- Studies have shown that epigenetic enzymes such as histone deacetylase (HDAC) are closely related to cancers and that several HDAC inhibitors exert antitumor effects. Studies have further suggested that class IIa HDAC inhibitors are related to immune functions, including immune responses and the expression of chemokines and complement pathway components. TMP195, a selective class IIa HDAC inhibitor, has been reported to be effective against breast cancer. However, the role and mechanism of TMP195 in colorectal cancer remain unknown. In this study, we found that TMP195 significantly reduced the tumor burden in two mouse models of colitis-associated colorectal cancer (CAC) and subcutaneous tumor. Mechanistically, TMP195 decreased the proportion of total macrophages but increased the proportion of M1 macrophages by promoting polarization, resulting in the increased release of inflammatory cytokines. TMP195 had no direct effect on the proliferation of colorectal cancer cells, and its antitumor effect on the colorectal cancer disappeared when macrophages were partly depleted by clodronate liposomes. In addition, TMP195 enhanced the efficacy of PD-1 blockade. The present study revealed that the combination of TMP195 and PD-1 blockade may provide a therapeutic strategy for colorectal cancer.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Mice
Animals
Programmed Cell Death 1 Receptor metabolism
Clodronic Acid metabolism
Clodronic Acid pharmacology
Liposomes metabolism
Liposomes pharmacology
Macrophages metabolism
Histone Deacetylases metabolism
Cytokines metabolism
Cell Line, Tumor
Histone Deacetylase Inhibitors pharmacology
Colorectal Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 18
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36263186
- Full Text :
- https://doi.org/10.7150/ijbs.73264