Interplay between the DNA Damage Response and Immunotherapy Response in Cancer

Int J Mol Sci. 2022 Nov 1;23(21):13356. doi: 10.3390/ijms232113356.

Abstract

Genome instability and immune evasion are both defining hallmarks of cancer. Tumorigenesis is frequently initiated when there is DNA damage to a proto-oncogene or tumor suppressor gene and DNA repair mechanisms are lost or insufficient to correct the damage; immune evasion then prevents the host immune system from recognizing these transformed cells. Therapies targeting genomic instability and immune evasion have been effectively used to treat cancer. Genotoxic therapies such as chemoradiation have been employed in cancer treatments for several decades, while immunotherapy is a relatively new class of cancer therapy that has led to disease regression even in patients with advanced cancer. Several recent studies have shown synergy between both classes of therapy targeting these two defining hallmarks of cancer, and different mechanisms are proposed to be involved. Here, we review the different classes of DNA damage, their links to cancer, and their contribution to immunotherapy responses, as well as the different models that are currently being used to study tumor-immune interactions.

Keywords: DNA repair; cancer; genome instability; immunotherapy.

Publication types

  • Review

MeSH terms

  • DNA Damage
  • DNA Repair
  • Genomic Instability
  • Humans
  • Immunotherapy*
  • Neoplasms* / genetics
  • Neoplasms* / therapy

Grants and funding

Research in the Lab of Cancer Epigenome is supported by the National Cancer Centre Research Fund, the Singapore Ministry of Health’s National Medical Research Council (NMRC) under its Singapore Translational Research Investigator Award (STaR) and National Research Foundation Singapore . K.S.L. is also supported by the Singapore Ministry of Health’s NMRC under its Open Fund Young Investigator Research Grant (OF-YIRG) .