ATM inhibition augments type I interferon response and antitumor T-cell immunity when combined with radiation therapy in murine tumor models.

ABSTRACT:

Background

Radiation therapy (RT) elicits DNA double-strand breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response via stimulator of interferon genes (STING) activation. We investigated whether combining RT with an ataxia-telangiectasia mutated inhibitor promoted these effects and amplified tumor immunity.

Methods

Mice-bearing syngeneic flank tumors (MOC2 head and neck squamous cell carcinoma or B78 melanoma) were treated with tumor-directed RT and oral administration of AZD0156. Specific immune cell depletion, type 1 interferon receptor 1 knock-out mice (IFNAR1-KO), and STING-deficient tumor cells were used to investigate tumor-immune crosstalk following RT and AZD0156 treatment.

Results

Combining RT and AZD0156 reduced tumor growth compared w

SUBMITTER: Jin WJ 

PROVIDER: S-EPMC10510866 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature