DNA Damage Repair in Brain Tumor Immunotherapy

Abstract

With the gradual understanding of tumor development, many tumor therapies have been invented and applied in clinical work, and immunotherapy has been widely concerned as an emerging hot topic in the last decade. It is worth noting that immunotherapy is nowadays applied under too harsh conditions, and many tumors are defined as "cold tumors" that are not sensitive to immunotherapy, and brain tumors are typical of them. However, there is much evidence that suggests a link between DNA damage repair mechanisms and immunotherapy. This may be a breakthrough for the application of immunotherapy in brain tumors. Therefore, in this review, first, we will describe the common pathways of DNA damage repair. Second, we will focus on immunotherapy and analyze the mechanisms of DNA damage repair involved in the immune process. Third, we will review biomarkers that have been or may be used to evaluate immunotherapy for brain tumors, such as TAMs, RPA, and other molecules that may provide a precursor assessment for the rational implementation of immunotherapy for brain tumors. Finally, we will discuss the rational combination of immunotherapy with other therapeutic approaches that have an impact on the DNA damage repair process in order to open new pathways for the application of immunotherapy in brain tumors, to maximize the effect of immunotherapy on DNA damage repair mechanisms, and to provide ideas and guidance for immunotherapy in brain tumors.

Keywords: DNA damage repair; ICI; TAMs; TME; biomarker; brain tumor; combination therapy; immunotherapy.

Figure 1

DNA damage repair pathway.

Figure 2

cGAS-STING pathway and ICI mechanism of action. In cGAS-STING pathway, cGAS binds to dsDNA and is subsequently activated to produce cGAMP. The latter interacts and activates STING on the endoplasmic reticulum membrane. STING then further confers TBK1 activity and sets the stage for TBK1 phosphorylation of IRF3, thus completing the recruitment of TBK1 and IRF3 by STING. Type I IFN is generated under the influence of IRF3 and functions to activate the immune system.