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.

Dual Targeting of DNA Damage Response Proteins Implicated in Cancer Radioresistance

“…IR causes a variety of DSB and non-DSB DNA lesions, which are processed by the appropriate pathways, and tumor radioresistance greatly depends on the ability of cancer cells to repair the IR-induced DNA damage [16]. Because of its critical role in DNA repair, RPA is believed to be involved in the effectiveness of radiotherapy [16] and could act as a potential biomarker for the preliminary assessment of immunotherapy in brain tumors like glioblastoma [61,62].…”

“…Molecular targets in DNA repair that are currently being investigated in pre-clinical and clinical trials include DNA PKcs, ATM, ATR, PARP, CHK1, and WEE1 [84]. Inhibition of these targets has been shown to confer to the radiosensitivity of tumor cells [61].…”

“…These findings could be extrapolated in the field of personalized precision medicine, taking into consideration the genetic profiling of cancer patients, towards co-administering this drug-like ligand agent with radiotherapy and/or other types of cancer treatment. Recent studies show that cancer therapies like radiotherapy and other types of therapies that damage DNA remodel the tumor immune microenvironment, offering the possibility of applying immunotherapy to tumors that are resistant to this type of therapy [61]. IR therapy promotes the release of tumor neoantigens during cancer cell death increasing the immunogenicity of the tumor, and it also promotes the activation of cytotoxic T-cells and dendritic cells [94,95].…”

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies

“…Unlike conventional tumor therapy, tumor immunotherapy is designed to recover the regular anti-tumor immune response by activating the tumor immune cycle for the detection and elimination of tumor cells. [4][5][6] Tumor immunotherapy is the fourth most common cancer treatment method after surgery, radiotherapy (RT) and chemotherapy. 7,8 Immunotherapy plays an essential part in the treatment of cancer by the activation or suppression of the immune system.…”