ArticleJournal for immunotherapy of cancer2016
Phenotypic and functional testing of circulating regulatory T cells in advanced melanoma patients treated with neoadjuvant ipilimumab.
Article in Journal for immunotherapy of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses 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
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
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.Melanoma research · 2019Pooled it
- Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma.Journal for immunotherapy of cancer · 2019Trial
- Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3Nature communications · 2024Article
- Immune Cell Profiling of Peripheral Blood as Signature for Response During Checkpoint Inhibition Across Cancer Types.Frontiers in oncology · 2021Article
- Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model.Scientific reports · 2019Article
- Therapeutic Monoclonal Antibodies Targeting Immune Checkpoints for the Treatment of Solid Tumors.Antibodies (Basel, Switzerland) · 2019Review
- Adjuvant Therapy for Melanoma.Current treatment options in oncology · 2019Review
- Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-α2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire.Journal for immunotherapy of cancer · 2018Article
- The Peripheral and Intratumoral Immune Cell Landscape in Cancer Patients: A Proxy for Tumor Biology and a Tool for Outcome Prediction.Biomedicines · 2018Review
- Biomarkers for Immune Checkpoint Inhibitors in Melanoma.Frontiers in oncology · 2018Review
- Association of Inflammatory Markers with Disease Progression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.The Permanente journal · 2018Article
- Biomarkers for Response of Melanoma Patients to Immune Checkpoint Inhibitors: A Systematic Review.Frontiers in oncology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe have previously investigated neoadjuvant ipilimumab (ipi) for patients with locally/regionally advanced melanoma. That initial assessment of peripheral blood mononuclear cells (PBMC) showed a significant increase in shared tumor associated antigen specific CD4(+) and CD8(+) T cell activation. We also observed a transient increase in circulating T regulatory cells (Treg) with a parallel increase in total CD4(+) T cells, as well as a significant decrease in circulating myeloid derived suppressor cells (MDSC). The increase in circulating Treg frequency, as assessed at 6 weeks after initiation of ipilimumab, was significantly associated with improved progression free survival (PFS, p = 0.034; HR = 0.57) and returned to baseline levels by 12 weeks. To shed light on the unexpected positive correlation between increased Treg and PFS, we here investigated the suppressive activity of circulating Treg at baseline and 6 weeks.
methodsPatients were treated with ipi (10 mg/kg intravenously every 3 weeks for 2 doses) bracketing definitive surgery. Treg (CD4(+)CD25(+)CD127(dim/-)) were isolated from pre-ipi (baseline) and post-ipi (6 weeks) PBMC samples. Treg were co-cultured with autologous responder CD4(+) T cells that were stimulated with OKT3/IL-2/CD28 and CFSE-labeled T cells. 1:1, 1:2, and 1:5 ratios were tested. Flow cytometery was used to evaluate the degree of Treg proliferation suppression.
resultsThirty-five patients were enrolled in the study; 18 patients had adequate PBMC samples with sufficient Treg isolated for Treg functional analysis. At 6 weeks following ipi, a decrease in percent of maximal inhibition of Th by Treg compared to baseline was seen for some patients. Scatter plot analysis showed no association between Treg frequency and function at any ratio or between circulating Treg frequency and function at baseline and at 6 weeks post-ipi. An increase in Treg suppressive function was significantly associated with a decrease in PFS (p = 0.02).
conclusionsWe find that Treg frequency measures do not correlate with suppressive activity measured ex vivo. Treg suppressive activity increases correlate with poorer patient outcomes.
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