ArticleNature communications2024
Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Longitudinal Analysis of Peripheral Blood CD4+ T-Cell Profiles and Clinical Outcomes in Metastatic Non-Small-Cell Lung Cancer Patients Following Bronchoscopic Cryotherapy and Pembrolizumab-Based Therapy.International journal of molecular sciences · 2026Trial
- Selective decay of interferon mRNAs controls antiviral immunity and innate memory.Molecular cell · 2026Article
- The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.Cancer immunology, immunotherapy : CII · 2026Review
- Cytokine Networks Reprogramming the Osteo-Immune Microenvironment in Cancer Bone Metastasis.Calcified tissue international · 2026Review
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Article
- GABRD promotes hepatocellular carcinoma progression via the IL-10RA/JAK2-STAT3 signaling axis.Cell death & disease · 2026Article
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Inflammatory cytokines induce new cancer dependencies.Nature genetics · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Loss of JAK1 Function Causes G2-M Cell-Cycle Defects Vulnerable to KIF18A Inhibition.Cancer research · 2026Article
- Stress-responsive membrane proteins as execution nodes of tumor cell adaptation to microenvironmental stress.Oncogene · 2026Review
- Predicting targeted- and immunotherapeutic response outcomes in melanoma with single-cell Raman spectroscopy and AI.bioRxiv : the preprint server for biology · 2026Article
- Single-cell profiling reveals MIF-mediated immune evasion and CD8 + T cell exhaustion in relapsed multiple myeloma.Clinical and experimental medicine · 2026Article
- Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas withBiomolecules & therapeutics · 2026Article
- TiRank prioritizes phenotypic niches in tumor microenvironment for clinical biomarker discovery.Genome medicine · 2026Article
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation.The British journal of dermatology · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Circulating cytokines as potential dynamic biomarkers of PD-1 blockade response and prognosis in non-small cell lung cancer.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Programmed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cancer cell-intrinsic PD-1 functional regulation is not well understood. Here, we demonstrate induction of PD-1 in melanoma cells via type I interferon receptor (IFNAR) signaling and reversal of ICB efficacy through IFNAR pathway inhibition. Treatment of melanoma cells with IFN-α or IFN-β triggers IFNAR-mediated Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling, increases chromatin accessibility and resultant STAT1/2 and IFN regulatory factor 9 (IRF9) binding within a PD-1 gene enhancer, and leads to PD-1 induction. IFNAR1 or JAK/STAT inhibition suppresses melanoma-PD-1 expression and disrupts ICB efficacy in preclinical models. Our results uncover type I IFN-dependent regulation of cancer cell-PD-1 and provide mechanistic insight into the potential unintended ICB-neutralizing effects of widely used IFNAR1 and JAK inhibitors.
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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 OpenQuestion graph.