Journal
BIOMEDICINES
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines10030557
Keywords
base excision repair; innate immune cells; innate inflammatory signaling; immunotherapy
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Funding
- National Institute of Health/National Cancer Center [R21CA 249346-01A1]
- AGA-R. Robert and Sally Funderburg of America Gastroenterology Association
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Innate immunity is crucial for recognizing and eliminating pathogens and inhibiting cancer cell growth. Dysregulation of innate immune systems can lead to inflammatory diseases and affect genomic integrity. DNA damage caused by oxidative stress is predominantly repaired by base excision repair (BER). Mutations in BER genes can result in impaired DNA repair function and insufficient genomic integrity. Accumulation of DNA damage may activate innate immune signaling and impact the interaction between cancer cells and innate immune cells.
Innate immunity is critical for immediate recognition and elimination of invading pathogens or defense against cancer cell growth. Dysregulation of innate immune systems is associated with the pathogenesis of different types of inflammatory diseases, including cancer. In addition, the maintenance of innate immune cells' genomic integrity is crucial for the survival of all organisms. Oxidative stress generated from innate immune cells may cause self-inflicted DNA base lesions as well as DNA damage on others neighboring cells, including cancer cells. Oxidative DNA base damage is predominantly repaired by base excision repair (BER). BER process different types of DNA base lesions that are presented in cancer and innate immune cells to maintain genomic integrity. However, mutations in BER genes lead to impaired DNA repair function and cause insufficient genomic integrity. Moreover, several studies have implicated that accumulation of DNA damage leads to chromosomal instability that likely activates the innate immune signaling. Furthermore, dysregulation of BER factors in cancer cells modulate the infiltration of innate immune cells to the tumor microenvironment. In the current review, the role of BER in cancer and innate immune cells and its impact on innate immune signaling within the tumor microenvironment is summarized. This is a special issue that focuses on DNA damage and cancer therapy to demonstrate how BER inhibitor or aberrant repair modulates innate inflammatory response and impact immunotherapy approaches. Overall, the review provides substantial evidence to understand the impact of BER in innate immune response dynamics within the current immune-based therapeutic strategy.
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