ArticleThe Journal of clinical investigation2021
Inhibiting the MNK1/2-eIF4E axis impairs melanoma phenotype switching and potentiates antitumor immune responses.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR.Cell death and differentiation · 2026Article
- NGFR induces melanoma invasion and immunotherapy resistance through myosin light chain 2 modulation.The EMBO journal · 2026Article
- Safety and efficacy of the MNK/VEGFR inhibitor JDB153 combined with the anti-PD-1 antibody serplulimab in patients with advanced pancreatic cancer refractory to standard treatment: a single-arm, phase Ib/II study protocol.Frontiers in pharmacology · 2026Article
- Hsa_circ_0000313/miR-1224-3p/MKNK2 Axis Modulates CD4Mediators of inflammation · 2026Article
- Lack of phospho-eIF4E worsens experimental colitis by inhibiting Treg suppressive activity.Journal of inflammation (London, England) · 2025Article
- SENP3 inhibition suppresses hepatocellular carcinoma progression and improves the efficacy of anti-PD-1 immunotherapy.Cell death and differentiation · 2025Article
- Guidelines for minimal reporting requirements, design and interpretation of experiments involving the use of eukaryotic dual gene expression reporters (MINDR).Nature structural & molecular biology · 2025Review
- eIF4F-mediated dysregulation of mRNA translation in cancer.RNA (New York, N.Y.) · 2025Review
- Anti-PD-1 amplifies costimulation in melanoma-infiltrating TJournal for immunotherapy of cancer · 2025Article
- Opportunities, obstacles and challenges of nano-immunotherapy in melanoma.Frontiers in immunology · 2025Review
- PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation.Life science alliance · 2024Article
- Second-Generation Cap Analogue Prodrugs for Targeting Aberrant Eukaryotic Translation Initiation Factor 4E (eIF4E) Activity in Drug-Resistant Melanoma.bioRxiv : the preprint server for biology · 2024Article
- Blocking tumor-intrinsic MNK1 kinase restricts metabolic adaptation and diminishes liver metastasis.Science advances · 2024Article
- Review
- MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.The Journal of clinical investigation · 2024Article
- M6A-related bioinformatics analysis indicates that LRPPRC is an immune marker for ischemic stroke.Scientific reports · 2024Article
- Tunable PhenoCycler imaging of the murine pre-clinical tumour microenvironments.Cell & bioscience · 2024Article
- The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy.MedComm · 2023Review
- A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.Journal of cellular and molecular medicine · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
33 authors at 6 institutions in 3 countries.
Funding
Abstract
Melanomas commonly undergo a phenotype switch, from a proliferative to an invasive state. Such tumor cell plasticity contributes to immunotherapy resistance; however, the mechanisms are not completely understood and thus are therapeutically unexploited. Using melanoma mouse models, we demonstrated that blocking the MNK1/2-eIF4E axis inhibited melanoma phenotype switching and sensitized melanoma to anti-PD-1 immunotherapy. We showed that phospho-eIF4E-deficient murine melanomas expressed high levels of melanocytic antigens, with similar results verified in patient melanomas. Mechanistically, we identified phospho-eIF4E-mediated translational control of NGFR, a critical effector of phenotype switching. Genetic ablation of phospho-eIF4E reprogrammed the immunosuppressive microenvironment, exemplified by lowered production of inflammatory factors, decreased PD-L1 expression on dendritic cells and myeloid-derived suppressor cells, and increased CD8+ T cell infiltrates. Finally, dual blockade of the MNK1/2-eIF4E axis and the PD-1/PD-L1 immune checkpoint demonstrated efficacy in multiple melanoma models regardless of their genomic classification. An increase in the presence of intratumoral stem-like TCF1+PD-1+CD8+ T cells, a characteristic essential for durable antitumor immunity, was detected in mice given a MNK1/2 inhibitor and anti-PD-1 therapy. Using MNK1/2 inhibitors to repress phospho-eIF4E thus offers a strategy to inhibit melanoma plasticity and improve response to anti-PD-1 immunotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.