ArticleThe Journal of experimental medicine2017
An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition.
Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
What it found
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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
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- Uncovering the Intricate and Heterogeneous Cellular Microenvironment of Cutaneous Melanoma.Medicina (Kaunas, Lithuania) · 2026Review
- Macrophage IL-1β turns meningeal fibroblasts into inflammatory amplifiers in pneumococcal infection.Frontiers in immunology · 2026Article
- Senescent Fibroblasts Drive Melanoma Progression Through GCP-2 Induced CREB Phosphorylation Enhancing Glycolysis.Aging cell · 2025Article
- Liposome-Polymer Nanoparticles Loaded with Copper Diethyldithiocarbamate and 6-Bromo-Indirubin-3'-Oxime Enable the Treatment of Refractive Melanoma.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- An update to experimental and clinical aspects of tumor-associated macrophages in cancer development: hopes and pitfalls.Clinical and experimental medicine · 2024Review
- Transcriptome-Wide Association Study Reveals New Molecular Interactions Associated with Melanoma Pathogenesis.Cancers · 2024Article
- Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment.Cell & bioscience · 2024Review
- Macrophage's role in solid tumors: two edges of a sword.Cancer cell international · 2023Article
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- Article
- BRAF V600-Mutated Metastatic Melanoma and Targeted Therapy Resistance: An Update of the Current Knowledge.Cancers · 2023Review
- Involvement of inflammasomes in tumor microenvironment and tumor therapies.Journal of hematology & oncology · 2023Review
- The NLRP3 inflammasome - interleukin 1β axis in uveal melanoma.FEBS open bio · 2023Article
- The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance.Oncogenesis · 2023Review
- Role of the tumor microenvironment in malignant melanoma organoids during the development and metastasis of tumors.Frontiers in cell and developmental biology · 2023Review
- IL-1RAP, a Key Therapeutic Target in Cancer.International journal of molecular sciences · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 9 institutions in 4 countries.
Funding
Abstract
Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive responses establish a mutation-independent drug tolerance. Antagonizing these adaptive responses could improve drug effects, thereby thwarting the emergence of acquired resistance. In this study, we reveal that inflammatory niches consisting of tumor-associated macrophages and fibroblasts contribute to treatment tolerance through a cytokine-signaling network that involves macrophage-derived IL-1β and fibroblast-derived CXCR2 ligands. Fibroblasts require IL-1β to produce CXCR2 ligands, and loss of host IL-1R signaling in vivo reduces melanoma growth. In tumors from patients on treatment, signaling from inflammatory niches is amplified in the presence of MAPK inhibitors. Signaling from inflammatory niches counteracts combined BRAF/MEK (MAPK/extracellular signal-regulated kinase kinase) inhibitor treatment, and consequently, inhibiting IL-1R or CXCR2 signaling in vivo enhanced the efficacy of MAPK inhibitors. We conclude that melanoma inflammatory niches adapt to and confer drug tolerance toward BRAF and MEK inhibitors early during treatment.
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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.