ArticleAmerican journal of cancer research2022
PD-L1 deficiency sensitizes tumor cells to DNA-PK inhibition and enhances cGAS-STING activation.
Article in American journal of cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 14 citations in OpenAlex.
- Galectin-9-driven immune evasion constrains radiotherapy-induced systemic antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- Current Perspectives on STING Agonists for Anticancer Drug Development.Chemical biology & drug design · 2026Review
- Unraveling the link between genomic instability and tumor immune evasion in oral squamous cell carcinoma: Role of CBMN assay and emerging perspectives.Medical oncology (Northwood, London, England) · 2026Review
- Dysregulation of the DNA repair‑immune axis: Targeted therapeutic strategies for autoimmune diseases (Review).International journal of molecular medicine · 2026Review
- Solamargin-functionalized gold nanoparticles codelivering photothermal-immunotherapy for triple-negative breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- Stiffness-dependent alveolar type II cell senescence in idiopathic pulmonary fibrosis.Cell communication and signaling : CCS · 2026Article
- Deciphering the Ubiquitin-like Code of DNA-PK: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- Rewired DDR-TGF-β-β-catenin-PD-L1 axis accelerates progression and shapes therapy in human papillomavirus-driven cancer.Frontiers in immunology · 2026Review
- Alterations and correlation between DNA damage and repair response and PD-L1 expression in non-small cell lung cancers.BMC cancer · 2025Article
- Anti-galectin-9 therapy synergizes with EGFR inhibition to reprogram the tumor microenvironment and overcome immune evasion.Journal for immunotherapy of cancer · 2025Article
- PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.Clinical and experimental medicine · 2025Review
- Article
- PD-L1 deglycosylation promotes its nuclear translocation and accelerates DNA double-strand-break repair in cancer.Nature communications · 2024Article
- Review
- Crosstalk between immune checkpoint and DNA damage response inhibitors for radiosensitization of tumors.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Targeting cGAS/STING signaling-mediated myeloid immune cell dysfunction in TIME.Journal of biomedical science · 2023Review
- Targeting the secreted RGDKGE collagen fragment reduces PD‑L1 by a proteasome‑dependent mechanism and inhibits tumor growth.Oncology reports · 2023Article
- Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity.International journal of biological sciences · 2023Article
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- Inhibition of Galectin-9 sensitizes tumors to anthracycline treatment via inducing antitumor immunity.International journal of biological sciences · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapies that block PD-L1/PD-1 immune checkpoint proteins represent a landmark breakthrough in cancer treatment. Although the role of PD-L1 in suppressing T cell activity has been extensively studied, its cancer cell-intrinsic functions are not well understood. Herein, we demonstrated that PD-L1 is important for the repair of DNA damage in cancer cells. Mechanically, depletion of PD-L1 led to the downregulation of the critical molecules involved in the homologous recombination (HR) repair pathway, such as ATM and BRCA1, but did not obviously affect the non-homologous end joining (NHEJ) pathway. Notably, PD-L1 silence sensitized cancer cells to chemotherapy agents and the inhibitor of DNA-PK, which is an important kinase for NHEJ. Furthermore, PD-L1 depletion potentiated DNA damage-induced cGAS-STING pathway and induction of IFNβ. The regulation of DNA repair and cGAS-STING pathway by PD-L1 represents its connection with innate immunity that can be exploited to enhance the efficacy of existing immunotherapy. Our findings thus expand the focus of PD-L1 from tumor antigen-specific CD8+ T cells to innate immunity, and support targeting tumor-intrinsic PD-L1 combined with DNA-PK inhibition for tumor eradication, through promoting synthetic lethality and innate immune response.
Indexed as
Identifiers
35693073PMC9185610W4285741471What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.