ArticleCell reports. Medicine2023
MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Genomic and Immune Landscape of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Progressing on Anti-PD-1 Treatment.Cancer immunology research · 2026Article
- Landscape and functional impact of variants of unknown significance of immune response genes in human cancer.Cancer gene therapy · 2026Article
- AGPAT3 reshapes tumor cell vulnerability to IFNγ-mediated ferroptosis and enhances immunotherapy efficacy through lipid remodeling.Journal for immunotherapy of cancer · 2026Article
- KAT2A Deficiency Suppresses Lung Cancer Progression by Downregulating MYC Through Decreasing MYC Succinylation.Cancer science · 2026Article
- Predicting neuroblastoma prognosis using machine learning analysis of metabolism-related gene network perturbation.BMC pediatrics · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.Frontiers in immunology · 2026Review
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- Integration of a novel anti-PD-1 antibody with chimeric antigen receptor-T engineered to express interleukin-7 enhances targeting efficacy against lung cancer.Life medicine · 2025Article
- Lactylation modification in lung cancer: A review of current research and future directions (Review).Oncology reports · 2025Review
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity.Autophagy · 2025Article
- Therapeutic Applications of Programmed Death Ligand 1 Inhibitors in Small Cell Lung Cancer.Biomedicines · 2025Review
- Potential role of lactylation in intrinsic immune pathways in lung cancer.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-γ (IFNγ), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNγ in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNγ-stimulated genes (IγSGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) deposition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNγ stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IγSGs stimulation by IFNγ. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNγ and may predict anti-PD1/L1 efficacy in LC.
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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.