Zhao Shengyuan, Habib Samy L, Senejani Alireza G, Sebastian Manu, Kidane Dawit
Division of Pharmacology and Toxicology, Dell Pediatric Research Institute, College of Pharmacy, The University of Texas at Austin, 1400 Barbara Jordan Blvd. R1800, Austin, TX 78723, USA.
Department of Cell Systems & Anatomy, University of Texas Health, San Antonio, TX 78229, USA.
Biomedicines. 2022 Feb 26;10(3):557. doi: 10.3390/biomedicines10030557.
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.
固有免疫对于立即识别和清除入侵病原体或抵御癌细胞生长至关重要。固有免疫系统的失调与包括癌症在内的不同类型炎症性疾病的发病机制相关。此外，维持固有免疫细胞的基因组完整性对于所有生物体的生存至关重要。固有免疫细胞产生的氧化应激可能导致自身DNA碱基损伤以及对包括癌细胞在内的其他邻近细胞的DNA损伤。氧化DNA碱基损伤主要通过碱基切除修复（BER）进行修复。BER处理癌症和固有免疫细胞中出现的不同类型的DNA碱基损伤，以维持基因组完整性。然而，BER基因的突变会导致DNA修复功能受损，并导致基因组完整性不足。此外，多项研究表明，DNA损伤的积累会导致染色体不稳定，这可能会激活固有免疫信号。此外，癌细胞中BER因子的失调会调节固有免疫细胞向肿瘤微环境的浸润。在本综述中，总结了BER在癌症和固有免疫细胞中的作用及其对肿瘤微环境中固有免疫信号的影响。这是一个专注于DNA损伤和癌症治疗的特刊，旨在展示BER抑制剂或异常修复如何调节固有炎症反应并影响免疫治疗方法。总体而言，该综述提供了大量证据，以了解BER在当前基于免疫的治疗策略中对固有免疫反应动态的影响。
