ArticleThe Journal of experimental medicine2024
PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.Nature medicine · 2026Trial
- Assessment of the Novel rVSV-PD-1-4-1BBL Oncolytic Activity on Mouse and Human Cancer Cell Lines.Biomedicines · 2026Article
- PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- DNA-damaging chemotherapy reshapes cardiac-resident macrophage composition and function.Science immunology · 2026Article
- Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Recent Progress and Emerging Trends.Current oncology (Toronto, Ont.) · 2025Review
- Opportunities, challenges, and future perspectives of oncolytic virus therapy for malignant melanoma.Frontiers in immunology · 2025Review
- T cell heterogeneity in asthma pathogenesis: from immunological mechanisms to biological targeted therapies.Frontiers in immunology · 2025Review
- Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.International journal of biological sciences · 2025Review
- Navigating the role of protein lactylation in prostate cancer and its implications for immunotherapy.Journal of Cancer · 2025Review
- Experimental models for developing oncolytic virotherapy for metastatic prostate cancer.Frontiers in immunology · 2025Review
- Arbutin overcomes tumor immune tolerance by inhibiting tumor programmed cell death-ligand 1 expression.International journal of medical sciences · 2024Article
- BRCA1 and BRCA2 deficient tumour models generate distinct ovarian tumour microenvironments and differential responses to therapy.Journal of ovarian research · 2023Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo. Consistently, PD-L1 expression marked tumor explants from cancer patients that were best infected by oncolytic viruses. Mechanistically, PD-L1 promoted a metabolic shift characterized by enhanced glycolysis rate that resulted in increased lactate production. In turn, lactate inhibited type I IFN responses. In addition to adding mechanistic insight into PD-L1 intrinsic function, our results will also help guide the numerous ongoing efforts to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.
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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 Socratic graph.