Trial reportInternational immunopharmacology2018
Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab.
Trial report in International immunopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02403778 (Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma), which is not on this map. Cited by 127 papers, 3 of them syntheses that pooled it.
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.
Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
Who cites it
127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Pooled it
- Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review.Frontiers in oncology · 2021Pooled it
- Neutrophil-driven immunosuppression in cancer.Cell insight · 2026Review
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Myeloid-Derived Suppressor Cells in Cancer: Metabolic Reprogramming, Immune Crosstalk, and Therapeutic Targeting.Cancers · 2026Review
- Retinoic Acid and Long Noncoding RNAs Crosstalk: Implications for Neuronal Differentiation and Diseases.Molecular neurobiology · 2026Review
- Review
- Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.Frontiers in immunology · 2026Review
- Synergistic Potential of Immune Checkpoint Inhibitor Combined with Neutrophil-Targeted Therapy in Cancer Immunotherapy.Research (Washington, D.C.) · 2026Review
- Myeloid-Derived Suppressor Cells and Radiotherapy: Regulation and Clinical Implications.Journal of Cancer · 2026Review
- Systemic administration of all-trans retinoic acid modulated circulating immune cells but failed to improve healing in a preclinical model of musculoskeletal trauma.Frontiers in immunology · 2026Article
- Human M-MDSCs impair neutrophil migration in the infectious microenvironment.Journal of leukocyte biology · 2025Article
- Significance of Vitamins A and E in Cancer Progression and Prevention.International journal of molecular sciences · 2025Review
- Review
- Insights into the relevance of targeting fibroblasts to control cancer.Cell reports. Medicine · 2025Review
- PMN-MDSCs are responsible for immune suppression in anti-PD-1 treated TAP1 defective melanoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy.Molecular cancer · 2025Review
- "Dissecting the role of T cell exhaustion in cancer progression: a multifaceted approach".Frontiers in immunology · 2025Review
- MDSC depletion during immunization with heat-killedFrontiers in immunology · 2025Article
67 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
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundImmune checkpoint inhibitors have improved overall survival rates for many cancers, yet the majority of patients do not respond to treatment and succumb to disease progression. One tumor-related mechanism limiting the efficacy of immunotherapies in melanoma is the recruitment and expansion of myeloid-derived suppressor cells (MDSCs). Therefore, targeting MDSCs in combination with immunotherapies is an attractive strategy to improve response rates and effectiveness.
methodsWe tested this strategy by designing a randomized phase II clinical trial treating advanced melanoma patients with either Ipilimumab monotherapy or Ipilimumab plus all-trans retinoic acid (ATRA). Clinicaltrails.gov identifier (NCT02403778). The frequency of circulating MDSCs and the activation of CD8(+) T cells was measured by flow cytometry. Expression of immunosuppressive genes was measured with quantitative real time-PCR. T cell suppressive functions were measured by mixed lymphocyte reaction.
resultsHere we show that in vitro treatment with ATRA decreases immunosuppressive function of MDSCs in mixed lymphocyte reactions. Additionally, ATRA reduces the expression of immunosuppressive genes including PD-L1, IL-10, and indoleamine 2,3‑dioxygenase by MDSCs. Furthermore, the addition of ATRA to standard of care Ipilimumab therapy appears safe, as ATRA did not increase the frequency of grade 3 or 4 adverse events. Finally, ATRA significantly decreased the frequency of circulating MDSCs compared to Ipilimumab treatment alone in advanced-stage melanoma patients.
conclusionsThese results illustrate the importance of MDSCs in immunotherapy resistance and provide evidence that targeting MDSCs in cancer patients may augment immunotherapeutic approaches.
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What Socratic holds
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 Socratic graph.