ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment.

ABSTRACT:

Purpose

ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor microenvironment.Experimental Design: We used an immunocompetent mouse model of HPV-driven malignancies to investigate the ATR inhibitor AZD6738 in combination with fractionated radiation (RT). Gene expression analysis and flow cytometry were performed posttherapy.

Results

Significant radiosensitization to RT by ATRi was observed alongside a marked increase in immune cell infiltration. We identified increased numbers of CD3⁺ and NK cells, but most of this infiltrate was composed of myeloid cells. ATRi plus radiation produced a gene expre

SUBMITTER: Dillon MT 

PROVIDER: S-EPMC6551222 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature