ArticleFrontiers in immunology2018
Interferon-α Up-Regulates the Expression of PD-L1 Molecules on Immune Cells Through STAT3 and p38 Signaling.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 96 citations in OpenAlex.
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- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- Opposing Association of Lung Neutrophils and PD-L1Aging cell · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Dermatomyositis predominates among checkpoint inhibitor-associated inflammatory myositis phenotypes: a pharmacovigilance disproportionality analysis identifies a class-wide signal.Rheumatology international · 2026Article
- Immune modulatory vaccines targeting tumor microenvironment antigens: recent advances in oncology and beyond.Signal transduction and targeted therapy · 2026Review
- Functional Type I and Type II interferon crosstalk restricts progenitor exhausted CD8 T cells through spatial exclusion and checkpoint enforcement.bioRxiv : the preprint server for biology · 2026Article
- Acute peritonitis-induced adipose CD127Nature communications · 2026Article
- Druggable genome CRISPR screening identifies the KEAP1/NRF2 axis as a mediator of PD-L1 expression.Communications biology · 2025Article
- Emerging cGAS-STING Agonist-Based Nanotherapeutics: Mechanistic Insights and Applications in Cancer Combination Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Improvement of the Anticancer Efficacy of PD-1/PD-L1 Blockade: Advances in Molecular Mechanisms and Therapeutic Strategies.MedComm · 2025Review
- Increased IFN responses drive myeloid cell activation in people living with HIV-1.Scientific reports · 2025Article
- Lipotoxicity, lipid peroxidation and ferroptosis: a dilemma in cancer therapy.Cell biology and toxicology · 2025Review
- Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Opaganib (ABC294640) Induces Immunogenic Tumor Cell Death and Enhances Checkpoint Antibody Therapy.International journal of molecular sciences · 2023Article
- Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19.Scientific reports · 2023Article
- Single-tailed heterocyclic carboxamide lipids for macrophage immune-modulation.Biomaterials science · 2023Article
- PD-L1: expression regulation.Blood science (Baltimore, Md.) · 2023Review
- Tumor microenvironment antigens.Seminars in immunopathology · 2023Review
- Therapeutically targeting type I interferon directly to XCR1+ dendritic cells reveals the role of cDC1s in anti-drug antibodies.Frontiers in immunology · 2023Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-α (IFNα) has one of the longest histories of use amongst cytokines in clinical oncology and has been applied for the treatment of many types of cancers. Due to its immune-activating properties, IFNα is also an attractive candidate for combinatory anti-cancer therapies. Despite its extensive use in animal tumor models as well as in several clinical trials, the different mechanisms underlying patient responses and affecting desirable clinical benefits are still under investigation. Here we show that in addition to its immune-activating properties, IFNα induces the expression of a key negative regulator, immunosuppressive PD-L1 molecule, in the majority of the specific immune cell populations, particularly in the dendritic cells (DC). DC can modulate immune responses by a variety of mechanisms, including expression of T-cell regulatory molecules and cytokines. Our results showed that treatment of DC with IFNα-2b led to pronounced up-regulation of surface expression of PD-L1 molecules, increased IL-6 and decreased IL-12 production. Moreover, we present evidence that IFNα-treated DC exhibited a reduced capacity to stimulate interferon-γ production in T cells compared to control DC. This T-cell response after treatment of DC with IFNα was recovered by a pre-treatment with an anti-PD-L1 blocking antibody. Further analyses revealed that IFNα regulated PD-L1 expression through the STAT3 and p38 signaling pathways, since blocking of STAT3 and p38 activation with specific inhibitors prevented PD-L1 up-regulation. Our findings underline the important roles of p38 and STAT3 in the regulation of PD-L1 expression and prove that IFNα induces STAT3/p38-mediated expression of PD-L1 and thereby a reduced stimulatory ability of DC. The augmentation of PD-L1 expression in immune cells through IFNα treatment should be considered by use of IFNα in an anti-cancer therapy.
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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.