Role of Base Excision Repair in Innate Immune Cells and Its Relevance for Cancer Therapy

Abstract

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.

Identification of PANoptosis-Based Prognostic Signature for Predicting Efficacy of Immunotherapy and Chemotherapy in Hepatocellular Carcinoma

“…It was found that high-risk population was mainly enriched in base excision repair (BER), cell cycle, mismatch repair, and other pathways ( Figure 8(c) ), while the low-risk group was mainly enriched in drug metabolism-cytochrome P450, fatty acid degradation, primary bile acid biosynthesis, tryptophan and tyrosine metabolism, and other pathways ( Figure 8(d) ). Three representative genes (NEIL2, OGG1, and APEX1) of BER were upregulated in high-risk population [ 15 ], confirming that patients with a high risk had more enriched BER activity (Supplementary Figure S4(b) ).…”

m6A methylation dynamically participates in the immune response againstVibrio anguillarumin half-smooth tongue sole (Cynoglossus semilaevis)

“…The BER pathway is primarily responsible for removing and repairing base lesions caused by oxidation, depurination, alkylation, and deamination, which help maintain the integrity of the genome under constant threat of environmental stresses (Stratigopoulou et al, 2020). Keeping genome integrity in immune cells is extremely important for their homeostasis, differentiation, and proliferation in response to internal and external stresses such as infection (Zhao et al, 2022). Except for its functions in DNA repair, BER pathway has been recently shown to regulate RNA metabolism and gene expression through transcriptional and post-transcriptional mechanisms (Antoniali et al, 2017), indicating this pathway may be a regulatory all-rounder.…”

Functional roles and cancer variants of the bifunctional glycosylase NEIL2

“…Reactive oxygen and nitrogen species produced by immune cells at sites of infection can induce DNA damage, and further amplify the inflammatory response. Dysfunctional DNA repair enzymes and dysregulation of DNA repair pathways can lead to the accumulation of DNA damage, and activation of innate immune signaling, suggesting a role for DNA repair proteins in the innate immune response (Kidane et al, 2014; Zhao et al, 2021; Zhao et al, 2022). NEIL2 is involved in the regulation of innate immunity via repair‐mediated regulation and repair‐independent regulation.…”