The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Abstract

Abstract As our understanding of the mechanisms of cancer treatment has increased, a growing number of studies demonstrate pathways through which DNA damage repair (DDR) affects the immune system. At the same time, the varied response of patients to immune checkpoint blockade (ICB) therapy has prompted the discovery of various predictive biomarkers and the study of combination therapy. Here, our investigation explores the interactions involved in combination therapy, accompanied by a review that summarizes currently identified and promising predictors of response to immune checkpoint inhibitors (ICIs) that are useful for classifying oncology patients. In addition, this work, which discusses immunogenicity and several components of the tumor immune microenvironment, serves to illustrate the mechanism by which higher response rates and improved efficacy of DDR inhibitors (DDRi) in combination with ICIs are achieved.

Keywords

• DNA damage repair
• DNA damage repair inhibitors
• Immune checkpoint inhibitor
• Immune checkpoint blockade
• cGAS/STING
• ATM/ATR/Chk1