ArticleNature immunology2024
Breaking NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection.
Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
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Who cites it
37 citing papers in PubMed, 43 citations in OpenAlex.
- Sensory innervation shapes cancer immunotherapy efficacy and adverse events.Journal for immunotherapy of cancer · 2026Review
- Review
- hUC-MSCs via β-NGF Alleviate Cognitive Impairment After Tibial Fracture Surgery by Regulating the STMN2/NMNAT2-SARM1-NF-κB Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- Understanding nerve-tumor interactions: From basic biology to therapeutic innovation.Genes & diseases · 2026Review
- Neuro-immune interactions in gastrointestinal oncology: Mechanisms, challenges, and therapeutic potential.Innovation (Cambridge (Mass.)) · 2026Review
- Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.International journal of molecular sciences · 2026Review
- Targeting ANXA1/TRKA axis enhances immunotherapy sensitivity in neural invasion-positive gastric cancer.Molecular biomedicine · 2026Article
- NGF-mediated tumor-stroma crosstalk promotes prostate cancer aggressiveness.Journal of translational medicine · 2026Article
- Mast-cell derived nerve growth factor drives ILC2 pro-tumoral functions in bladder cancer.Nature communications · 2026Article
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- Exogenous Epstein-Barr virus nuclear antigen 1 induces ADAR1-driven tumor resistance against immunotherapy.Signal transduction and targeted therapy · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- The Immune Biology of the Adrenal Gland Microenvironment and Its Role in Metastatic Progression.International journal of molecular sciences · 2026Review
- Neuro-immune interactions in cancer: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- A bittersweet symphony: soluble mediator networks orchestrate melanoma plasticity and therapeutic adaptation.Frontiers in cell and developmental biology · 2026Review
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian cancer models.Journal for immunotherapy of cancer · 2025Article
- Exploration of the roles of CAFs in melanoma based on single-cell transcriptomics and spatial transcriptomics.Discover oncology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF engages tropomyosin receptor kinase A (TrkA) on melanoma cells to desensitize interferon γ signaling, leading to T and natural killer cell exclusion. In effector T cells that upregulate surface TrkA expression upon T cell receptor activation, paracrine NGF dampens T cell receptor signaling and effector function. Inhibiting NGF, either through genetic modification or with the tropomyosin receptor kinase inhibitor larotrectinib, renders melanomas susceptible to immune checkpoint blockade therapy and fosters long-term immunity by activating memory T cells with low affinity. These results identify the NGF-TrkA axis as an important suppressor of anti-tumor immunity and suggest larotrectinib might be repurposed for immune sensitization. Moreover, by enlisting low-affinity T cells, anti-NGF reduces acquired resistance to immune checkpoint blockade and prevents melanoma recurrence.
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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.