DNA damage repair and cancer immunotherapy

Abstract

Cells are exposed to multiple endogenous and exogenous stresses daily, some of which can induce DNA damage, a major source of genomic instability. To deal with damaged DNA and maintain genomic integrity, cells have evolved complicated DNA damage repair (DDR) machinery. Impaired DDR pathways can lead to the accumulation of DNA damage and genomic instability, a risk factor for carcinogenesis. If cancer occurs, DDR is normally associated with increased survival of tumor cells and the development of treatment resistance. Increasingly, evidence shows that the activity of DDR pathways not only impact the outcomes of cytotoxic treatments, but also multiple aspects of anti-tumor immunity. As such, DDR deficiency is emerging as a promising prognostic factor in predicting the therapeutic outcomes of immunotherapy. Accordingly, modulation of DDR pathways can improve immunotherapeutic efficiency in cancer treatment. In this review, we outline the mechanisms of DNA damage, the DDR pathways which counteract them and summarize the association between altered DDR pathways and cancer. Additionally, we highlight DDR deficiency in the context of cancer immunity, and its potential applications in the combined treatment of cancer.

Funding

Interdisciplinary Research Foundation of HIT, National Nature Science Foundation(82025027)

Nature Science Foundation of Heilongjiang Province(YQ2021C024)