Dual-Epigenetically Relieving the MYC-Correlated Immunosuppression via an Advanced Nano-Radiosensitizer Potentiates Cancer Immuno-Radiotherapy.
Adv Mater
; 36(19): e2312588, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38316447
ABSTRACT
Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Radiation-Sensitizing Agents
/
Proto-Oncogene Proteins c-myc
/
Epigenesis, Genetic
/
Immunotherapy
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Mater
/
Adv. mater. (Weinheim Print)
/
Advanced materials (Weinheim Print)
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Alemania