DNA Repair Deficiency Regulates Immunity Response in Cancers: Molecular Mechanism and Approaches for Combining Immunotherapy

Author:

Xu Yi1,Nowsheen Somaira2ORCID,Deng Min1

Affiliation:

1. State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

2. Department of Dermatology, University of California San Diego, San Diego, CA 92122, USA

Abstract

Defects in DNA repair pathways can lead to genomic instability in multiple tumor types, which contributes to tumor immunogenicity. Inhibition of DNA damage response (DDR) has been reported to increase tumor susceptibility to anticancer immunotherapy. However, the interplay between DDR and the immune signaling pathways remains unclear. In this review, we will discuss how a deficiency in DDR affects anti-tumor immunity, highlighting the cGAS-STING axis as an important link. We will also review the clinical trials that combine DDR inhibition and immune-oncology treatments. A better understanding of these pathways will help exploit cancer immunotherapy and DDR pathways to improve treatment outcomes for various cancers.

Funder

Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences

the CAMS Innovation Fund for Medical Sciences

the National Natural Science Foundation of China

Beijing Hope Run Special Fund of Cancer Foundation of China

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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