Trial reportJournal for immunotherapy of cancer2022
Improved prognosis and evidence of enhanced immunogenicity in tumor and circulation of high-risk melanoma patients with unknown primary.
Trial report in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
What it found
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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
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Pooled it
- Melanoma of unknown primary: a comprehensive review of immune-mediated pathogenesis and therapies.The oncologist · 2025Pooled it
- Article
- Predicting immune-related thyroiditis using polygenic risk scores in patients with advanced melanoma.Journal for immunotherapy of cancer · 2026Article
- Case Report: Exceptional response to perioperative pembrolizumab in UV-signature melanoma of unknown primary presenting as an isolated pulmonary metastasis.Frontiers in oncology · 2026Article
- The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.Cancer research communications · 2024Article
- Integrative analysis of single-cell and bulk RNA sequencing unveils a machine learning-based pan-cancer major histocompatibility complex-related signature for predicting immunotherapy efficacy.Cancer immunology, immunotherapy : CII · 2024Article
- The tumor microbiome as a predictor of outcomes in patients with metastatic melanoma treated with immune checkpoint inhibitors.bioRxiv : the preprint server for biology · 2023Article
- Suitability of tumor-associated antibodies as predictive biomarker for response to immune checkpoint inhibitors in patients with melanoma: a short report.Journal for immunotherapy of cancer · 2023Article
- Systematic evaluation of the predictive gene expression signatures of immune checkpoint inhibitors in metastatic melanoma.Molecular carcinogenesis · 2023Article
- HEV-associated dendritic cells are observed in metastatic tumor-draining lymph nodes of cutaneous melanoma patients with longer distant metastasis-free survival after adjuvant immunotherapy.Frontiers in immunology · 2023Article
- Enhanced immune activation within the tumor microenvironment and circulation of female high-risk melanoma patients and improved survival with adjuvant CTLA4 blockade compared to males.Journal of translational medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundMelanoma of unknown primary (MUP) represents a poorly understood group of patients both clinically and immunologically. We investigated differences in prognosis and candidate immune biomarkers in patients with unknown compared with those with known primary melanoma enrolled in the E1609 adjuvant trial that tested ipilimumab at 3 and 10 mg/kg vs high-dose interferon-alfa (HDI). PATIENTS AND
methodsMUP status was defined as initial presentation with cutaneous, nodal or distant metastasis without a known primary. Relapse-free survival (RFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method. Stratified (by stage) log-rank test was used to compare RFS and OS by primary tumor status. Gene expression profiling (GEP) was performed on the tumor biopsies of a subset of patients. Similarly, peripheral blood samples were tested for candidate soluble and cellular immune biomarkers.
resultsMUP cases represented 12.8% of the total population (N=1699) including 11.7% on the ipilimumab arms and 14.7% on the HDI arm. Stratifying by stage, RFS (p=0.001) and overall survival (OS) (p=0.009) showed outcomes significantly better for patients with unknown primary. The primary tumor status remained prognostically significant after adjusting for treatment and stage in multivariate Cox proportional hazards models. Including only ipilimumab-treated patients, RFS (p=0.005) and OS (p=0.023) were significantly better in favor of those with unknown primary. Among patients with GEP data (n=718; 102 MUP, 616 known), GEP identified pathways and genes related to autoimmunity, inflammation, immune cell infiltration and immune activation that were significantly enriched in the MUP tumors compared with known primaries. Further investigation into infiltrating immune cell types estimated significant enrichment with CD8 +and CD4+T cells, B cells and NK cells as well as significantly higher major histocompatibility complex (MHC)-I and MHC-II scores in MUP compared with known primary. Among patients tested for circulating biomarkers (n=321; 66 unknown and 255 known), patients with MUP had significantly higher circulating levels of IL-2R (p=0.04).
conclusionPatients with MUP and high-risk melanoma had significantly better prognosis and evidence of significantly enhanced immune activation within the TME and the circulation, supporting the designation of MUP as a distinct prognostic marker in patients with high-risk melanoma.
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