Base excision repair regulates PD-L1 expression in cancer cells

Permata, Tiara Bunga Mayang; Hagiwara, Yoshihiro; Sato, Hiro; Yasuhara, Takaaki; Oike, Takahiro; Gondhowiardjo, Soehartati; Held, Kathryn D.; Nakano, Takashi; Shibata, Atsushi

doi:10.1038/s41388-019-0733-6

Cited by 83 publications

(71 citation statements)

References 54 publications

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“…Oxidative stress causes SSB and base damage, which are repaired by SSB repair and BER, respectively. Furthermore, depletion of NTH1, a central component of BER, increases the upregulation of PD‐L1 expression in response to oxidative stress, supporting the notion that DNA damage signaling induced by oxidative stress upregulates PD‐L1 . Similar to the events at DSBs, ATR/Chk1 signaling is required for the upregulation of PD‐L1 expression after oxidative DNA damage.…”

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 53%

“…Similar to the events at DSBs, ATR/Chk1 signaling is required for the upregulation of PD‐L1 expression after oxidative DNA damage. However, because oxidative DNA damage does not directly introduce DSBs, we hypothesize that ATR/Chk1 signaling is activated after oxidative DNA damage through replication‐associated DNA damage in S phase . As ATR/Chk1 can be activated at single‐strand gaps during the stalling of DNA replication, replication stress induced by oxidative stress could also be involved in the upregulation of PD‐L1 irrespective of direct DSB induction.…”

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 99%

“…Several recent studies reported that DNA damage induces the expression of PD‐L1 mRNA, which results in the increase in the cell surface expression of PD‐L1 . This process depends on the activity of the ATM‐ATR/Chk1 signal transduction, suggesting that the expression of PD‐L1 is controlled by DNA damage signaling.…”

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 99%

“…Moreover, we recently found that oxidative DNA damage upregulates cell surface PD‐L1 expression in cancer cells . Oxidative stress causes SSB and base damage, which are repaired by SSB repair and BER, respectively.…”

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 99%

“…Although the number of microsatellite sequences can change during DNA replication, MMR is able to correct not only mispaired bases but also insertions and deletions; therefore, lack of MMR activity causes aberrations in microsatellite repeats, resulting in an increase in genome‐wide MSI. Interestingly, tumors with mutations in BER genes also show a high frequency of MSI, and BER‐deficient tumors express higher levels of neoantigens and PD‐L1 . If BER deficiency fails to remove an alkylated or an oxidized base, it could cause mispairing throughout the genome, including microsatellite sequences.…”

Section: Regulation Of Pd‐l1 Expression In Tumors In the Context Of Mmentioning

confidence: 99%

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Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

2019

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Anti‐programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) therapy, which is one of the most promising cancer therapies, is licensed for treating various tumors. Programmed death‐ligand 1, which is expressed on the surface of cancer cells, leads to the inhibition of T lymphocyte activation and immune evasion if it binds to the receptor PD‐1 on CTLs. Anti‐PD‐1/PD‐L1 Abs inhibit interactions between PD‐1 and PD‐L1 to restore antitumor immunity. Although certain patients achieve effective responses to anti‐PD‐1/PD‐L1 therapy, the efficacy of treatment is highly variable. Clinical trials of anti‐PD‐1/PD‐L1 therapy combined with radiotherapy/chemotherapy are underway with suggestive evidence of favorable outcome; however, the molecular mechanism is largely unknown. Among several molecular targets that can influence the efficacy of anti‐PD‐1/PD‐L1 therapy, PD‐L1 expression in tumors is considered to be a critical biomarker because there is a positive correlation between the efficacy of combined treatment protocols and PD‐L1 expression levels. Therefore, understanding the mechanisms underlying the regulation of PD‐L1 expression in cancer cells, particularly the mechanism of PD‐L1 expression following DNA damage, is important. In this review, we consider recent findings on the regulation of PD‐L1 expression in response to DNA damage signaling in cancer cells.

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Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 53%

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 99%

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 99%

Section: Regulation Of Pd‐l1 Expression In Response To Dna Damage Sigmentioning

confidence: 99%

Section: Regulation Of Pd‐l1 Expression In Tumors In the Context Of Mmentioning

confidence: 99%

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Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

2019

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A Trojan Horse Delivery Vehicle Carrying siRNA Nanotherapeutics with Multiple Tumor Microenvironment Responsiveness Elicits Robust Antitumor Immune Responses In Situ via a “Self‐Synergistic” Approach

Fang

Chen

Zhang

et al. 2023

Adv Healthcare Materials

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The potential of small interfering RNAs (siRNAs) in the treatment of malignant tumors has attracted increasing attention due to their inherent advantages. However, their therapeutic performance strongly depends on the efficiency of their cytoplasmic delivery in vivo by the delivery vehicle with good cellular permeability and histocompatibility. Herein, a polycationic carrier camouflaged with macrophage membrane was constructed biomimetically, which was condensed from endogenous spermine monomers through diselenide bonds. The developed Trojan horse delivery vehicle has desirable compression efficacy for siPDL1 as well as intracytoplasmic release properties derived from its sequential degradation triggered by redox microenvironment in tumor cells. Further, the co‐loading of photosensitizer could mediate PDT accompanied by the generation of reactive oxygen species (ROS) upon light irradiation applied, which accelerated the degradation of the carrier as well as the release of cargoes while enhancing the PDL1 blockage‐mediated immunotherapy by inducing in situ immunogenic cell death. Moreover, the synchronously delivered siPDL1 attenuated the ROS‐induced increase in immunosuppressive PDL1 expression, thereby effectively eliciting a robust antitumor immune response with a “self‐synergistic” manner in the xenograft breast cancer mouse model.This article is protected by copyright. All rights reserved

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Mechanisms of immunogenic cell death and immune checkpoint blockade therapy

Lin

2021

The Kaohsiung J of Med Scie

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Immunogenic cell death (ICD) refers to a form of regulated cell death that activates adaptive immunity, forming long-term immunological memory. Using chemotherapeutic drugs to induce ICD in cancer cells can help create an inflamed, immunogenic tumor environment, key for optimal immune checkpoint blockade (ICB) therapy response. ICB targets immune checkpoints such as cytotoxic T-lymphocyteassociated antigen 4 (CTLA4) and programmed death 1 (PD-1). Durable responses and better quality of life in ICB patients compared with many other treatments has prompted additional investigation into its therapeutic potential and possible approaches, in an effort to further understand the functions of the costimulatory molecules and how new treatments may be designed. In this review, we will summarize ICD induction, including stress responses, damage-associated molecular patterns, and various assays by which immunogenicity is evaluated in dying cells. In addition, the mechanisms and biomarkers underlying the CTLA4 and PD-1 pathways of checkpoint blockade will be covered. Finally, we will review the synergistic effects of ICD induction combined with ICB therapy, as well as combination blockade therapies involving the use of multiple drugs.

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Base excision repair regulates PD-L1 expression in cancer cells

Cited by 83 publications

References 54 publications

Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

A Trojan Horse Delivery Vehicle Carrying siRNA Nanotherapeutics with Multiple Tumor Microenvironment Responsiveness Elicits Robust Antitumor Immune Responses In Situ via a “Self‐Synergistic” Approach

Mechanisms of immunogenic cell death and immune checkpoint blockade therapy

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