Targeting DNA Repair, Cell Cycle, and Tumor Microenvironment in B Cell Lymphoma

Bröckelmann, Paul J.; Jong, Mathilde Rikje Willemijn de; Jachimowicz, Ron D.

doi:10.3390/cells9102287

Cited by 16 publications

(15 citation statements)

References 99 publications

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“…Also, targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), PARPi combined with anti-CTLA-4 antibodies has demonstrated similar effects [ 127 , 128 ]. Apart from immune checkpoint blockade therapy, chimeric antigen receptor T cell (CAR-T) immunotherapy has not been applied to solid tumors.…”

Section: The Effect Of Altered Ddr Pathway Interactions On Icismentioning

confidence: 99%

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The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Shi

Qin

Lin

et al. 2022

J Exp Clin Cancer Res

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As our understanding of the mechanisms of cancer treatment has increased, a growing number of studies demonstrate pathways through which DNA damage repair (DDR) affects the immune system. At the same time, the varied response of patients to immune checkpoint blockade (ICB) therapy has prompted the discovery of various predictive biomarkers and the study of combination therapy. Here, our investigation explores the interactions involved in combination therapy, accompanied by a review that summarizes currently identified and promising predictors of response to immune checkpoint inhibitors (ICIs) that are useful for classifying oncology patients. In addition, this work, which discusses immunogenicity and several components of the tumor immune microenvironment, serves to illustrate the mechanism by which higher response rates and improved efficacy of DDR inhibitors (DDRi) in combination with ICIs are achieved.

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Section: The Effect Of Altered Ddr Pathway Interactions On Icismentioning

confidence: 99%

“…Aging-related secretory phenotypes function to recruit innate immune cells, including NK cells and macrophages, as well as CD8 + T cells [127]. Instability of aneuploid accumulation after chromosome separation into the micronucleus can directly up-regulate senescence-associated secretory phenotypes (SASP) [189][190][191].…”

Section: Innate Immune Cellmentioning

confidence: 99%

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Shi

Qin

Lin

et al. 2022

J Exp Clin Cancer Res

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“…The effect of anti-cancer agents on cell-cycle progression is important. Most, if not all, human cancer types show a deregulated control of G1 progression, a period in which cells decide whether to begin proliferation or stay quiescent [ 46 ]. In the cell-cycle analysis, we observed that CH-AuNPs did not induce cell-cycle alterations in HUVECs, similar to our observations in tumor (HeLa and MCF-7) [ 17 ] and leukemic (K562 and CEM) [ 18 ] cell lines.…”

Section: Discussionmentioning

confidence: 99%

Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status

et al. 2021

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(1) Background: Chitosan-coated gold nanoparticles (CH-AuNPs) have important theranostic applications in biomedical sciences, including cancer research. However, although cell cytotoxicity has been studied in cancerous cells, little is known about their effect in proliferating primary leukocytes. Here, we assessed the effect of CH-AuNPs and the implication of ROS on non-cancerous endothelial and fibroblast cell lines and in proliferative lymphoid cells. (2) Methods: The Turkevich method was used to synthetize gold nanoparticles. We tested cell viability, cell death, ROS production, and cell cycle in primary lymphoid cells, compared with non-cancer and cancer cell lines. Concanavalin A (ConA) or lipopolysaccharide (LPS) were used to induce proliferation on lymphoid cells. (3) Results: CH-AuNPs presented high cytotoxicity and ROS production against cancer cells compared to non-cancer cells; they also induced a different pattern of ROS production in peripheral blood mononuclear cells (PBMCs). No significant cell-death difference was found in PBMCs, splenic mononuclear cells, and bone marrow cells (BMC) with or without a proliferative stimuli. (4) Conclusions: Taken together, our results highlight the selectivity of CH-AuNPs to cancer cells, discarding a consistent cytotoxicity upon proliferative cells including endothelial, fibroblast, and lymphoid cells, and suggest their application in cancer treatment without affecting immune cells.

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“…The ATM gene encodes a protein that is an important cell cycle checkpoint kinase that phosphorylates important sites such as CHK2, p53, MRN complex and plays a prominent role in the HR pathway ( 83 ). ATM, an important factor in DNA damage repair, signals in association with PARP-1 to activate E3 ubiquitin ligase within one hour of recognition of a DNA double-strand break.…”

Section: Targeted Dna Damage Repair To Explore Immunotherapy Biomarkermentioning

confidence: 99%

“…The ATM gene encodes a protein that is an important cell cycle checkpoint kinase that phosphorylates important sites such as CHK2, p53, MRN complex and plays a prominent role in the HR pathway (83) and in this way enhance the effect of ICI treatment. Therefore, mutations in ATM can be used to predict the clinical efficacy of ICI as an ICI therapeutic target and biomarker (87).…”

Section: Atmmentioning

confidence: 99%

DNA Damage Repair in Brain Tumor Immunotherapy

Zhao

et al. 2022

Front. Immunol.

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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.

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Targeting DNA Repair, Cell Cycle, and Tumor Microenvironment in B Cell Lymphoma

Cited by 16 publications

References 99 publications

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status

DNA Damage Repair in Brain Tumor Immunotherapy

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