The Role of HDAC6 Inhibitors (HDAC6i) on CD47/SIRPa Pathway in Human Melanoma

CD47 is ubiquitously expressed on the surface of cancer cells. Its interaction with SIRPa on macrophages' surfaces inhibits the phagocytic activity of macrophages. Epigenetics has a role to play in cancers that are resistant to immunotherapy. Recent studies show that HDAC6 was a modulator of the expression of CD47 and SIRPa in Melanoma, and macrophages are considered potential targets for cancer immunotherapy. Therefore, further investigation on the modulation of CD47 and macrophage phenotype by epigenetic modifiers is needed.Herein, a highly specific HDAC6i, Nexturastat A (NextA), was used and has been confirmed to decrease the pro-tumorigenic M2 macrophages phenotype and impact CD47/SIRPa axis in Melanoma. Our results indicated that the combination of NextA and IFNy treatment showed profound changes in the tumor microenvironment (TME), such as a significant downregulation of the expression of CD47 in human Melanoma cells and reduction in SIRPa expression in macrophages after IFNy treatment in different types of cancer cells. This finding could give a potential preclinical efficacy for future studies to use HDAC6is as immunomodulatory agents.

Author

• Alahmadi, Zubaydah

Language

• en

Keyword

• HDAC6
• immunecheckpoint
• SIRPa
• Melanoma
• CD47
• immunotherapy

Date created

• 2022

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Bioinformatics and Molecular Biochemistry

Degree

• M.S.

Advisor

• Villagra, Alejandro
• Vanderhoek, Jack

Committee Member(s)

• Shook, Brett

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/8336h275p