ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Evidence of systemic Th2-driven chronic inflammation in patients with metastatic melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 171 citations in OpenAlex.
- IL-12p70-producing patient DC vaccine elicits Tc1-polarized immunity.The Journal of clinical investigation · 2013Trial
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- Baseline Red Blood Cell Distribution Width as a Prognostic Marker in High-Risk Resected Cutaneous Melanoma.Journal of clinical medicine · 2026Article
- Tongue cancer in pregnancy: challenges and outcomes. A case series and review of the literature.Oral and maxillofacial surgery · 2025Review
- mRNA therapeutics: Transforming medicine through innovation in design, delivery, and disease treatment.Molecular therapy. Nucleic acids · 2025Review
- Multi-Modal Biomarker Profiling of Tumor Microenvironment and Genomic Alterations to Enhance Immunotherapy Stratification in Melanoma.Current issues in molecular biology · 2025Article
- Pan-cancer analysis reveals ASCC family promotes the cancer progression of lung adenocarcinoma.Scientific reports · 2025Article
- Phase I study of pembrolizumab in combination with ibrutinib for the treatment of unresectable or metastatic melanoma.Frontiers in immunology · 2025Article
- Th17 cell function in cancers: immunosuppressive agents or anti-tumor allies?Cancer cell international · 2024Review
- Failed Induction of the TIntegrative medicine (Encinitas, Calif.) · 2024Article
- Peripheral immune cells in metastatic breast cancer patients display a systemic immunosuppressed signature consistent with chronic inflammation.NPJ breast cancer · 2024Article
- Targeting MELK improves PD-1 blockade efficiency in cervical cancer via enhancing antitumor immunity.Molecular therapy. Oncology · 2024Article
- Melanoma-derived cytokines and extracellular vesicles are interlinked with macrophage immunosuppression.Frontiers in molecular biosciences · 2024Article
- New insights into the correlations between circulating tumor cells and target organ metastasis.Signal transduction and targeted therapy · 2023Review
- JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer.Cancers · 2023Article
- A pan-cancer analysis of the oncogenic role of Golgi transport 1B in human tumors.Journal of translational internal medicine · 2023Article
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
- Melanoma-derived mediators can foster the premetastatic niche: crossroad to lymphatic metastasis.Trends in immunology · 2023Review
- Health Consequences of Thymus Removal in Adults.The New England journal of medicine · 2023Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeImmunotherapeutic modalities are commonly used for treatment of patients with melanoma. The therapeutic success in preclinical models has not yielded the expected clinical results. To understand this discrepancy, we attempted to define immune homeostasis of 209 patients with melanoma across stages of disease relative to normal controls. EXPERIMENTAL
designPeripheral blood mononuclear cells (PBMC) and plasma were collected from patients and healthy donors. PBMC were analyzed for frequencies of natural killer, dendritic, and T cells and their functional status. Matched plasma samples were analyzed for the concentrations of 27 cytokines, chemokines, and growth factors. RNA was isolated from 24 metastatic melanoma tumor biopsies and profiled by microarray analysis.
resultsThe frequency of natural killer, T, and dendritic cells in patients does not significantly change across stages of melanoma. However, plasma concentrations of Th2 cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] in tumor-bearing patients were significantly higher than those with resected melanoma. Expression array analysis of metastatic melanoma revealed that the malignant melanocytes were not the source of the Th2 cytokines but did highly up-regulate vascular endothelial growth factor (VEGF) transcripts, consistent with plasma VEGF concentrations. In vitro VEGF exposure of normal PBMC lead to repolarization from Th1 to Th2 emulating the state of metastatic melanoma.
conclusionsPatients with metastatic melanoma exist in a state of Th2-mediated "chronic inflammation" as a result of at least VEGF overproduction by malignant tumors. These data support prior observations regarding the effect of VEGF on immune cell function and suggests consideration of VEGF inhibitors in future cancer immunotherapy clinical studies in metastatic melanoma.
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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.