ArticleProceedings of the National Academy of Sciences of the United States of America2021
PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Temporal Dynamics of PD-L1 Surface in RKO Cells: Characterizing the Reversible Impact of the Small-Molecule Dimerizer BMS-202.Biomedicines · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- PTPN2 inhibition unleashes response to STING agonism in head and neck squamous cell cancer.Nature communications · 2026Article
- IFN signaling at the nexus of the radiotherapy response in malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Rewired DDR-TGF-β-β-catenin-PD-L1 axis accelerates progression and shapes therapy in human papillomavirus-driven cancer.Frontiers in immunology · 2026Review
- Avelumab induces greater Fc-Fc receptor-dependent natural killer cell activation and dendritic cell crosstalk compared to durvalumab.Oncoimmunology · 2025Article
- Targeting DNA Damage Response and Immune Crosstalk in Cancer: Mechanistic Insights and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- BLID is a drug-responsive target of FOXO3a and multi-omics analysis reveals survival mechanisms and therapeutic vulnerabilities in BLID-deficient breast cancer cells.Oncology letters · 2025Article
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- Cancer cell-extrinsic STING shapes immune-active microenvironment and predicts clinical outcome in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges.Essays in biochemistry · 2025Review
- Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6/Jak/Stat3 in PD-L1-high lung cancer.Journal for immunotherapy of cancer · 2025Article
- Article
- A phase Ib/II study of modakafusp alfa alone and in combination with pembrolizumab in patients with advanced or metastatic solid tumors.Frontiers in oncology · 2025Article
- Uncovering the role of tumor cGAS expression in predicting response to PD-1/L1 inhibitors in non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Article
- PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.The Journal of experimental medicine · 2024Article
- Epithelial-mesenchymal transition induced by tumor cell-intrinsic PD-L1 signaling predicts a poor response to immune checkpoint inhibitors in PD-L1-high lung cancer.British journal of cancer · 2024Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Programmed death ligand 1 (PD-L1), an immune-checkpoint protein expressed on cancer cells, also functions independently of the immune system. We found that PD-L1 inhibits the killing of cancer cells in response to DNA damage in an immune-independent manner by suppressing their acute response to type I interferon (IFN; IFN-I). In addition, PD-L1 plays a critical role in sustaining high levels of constitutive expression in cancer cells of a subset of IFN-induced genes, the IFN-related DNA damage resistance signature (IRDS) which, paradoxically, protects cancer cells. The cyclic GMP-AMP synthase-stimulator of the IFN genes (cGAS-STING) pathway is constitutively activated in a subset of cancer cells in the presence of high levels of PD-L1, thus leading to a constitutive, low level of IFN-β expression, which in turn increases IRDS expression. The constitutive low level of IFN-β expression is critical for the survival of cancer cells addicted to self-produced IFN-β. Our study reveals immune-independent functions of PD-L1 that inhibit cytotoxic acute responses to IFN-I and promote protective IRDS expression by supporting protective chronic IFN-I responses, both of which enhance the resistance of cancer cells to DNA damage.
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