ArticleJournal of translational medicine2022
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.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01274338 (A Phase III Randomized Study of Adjuvant Ipilimumab Anti-CTLA4 Therapy Versus High Dose Interferon a-2b for Resected High Risk Melanoma), which is not on this map. Cited by 6 papers.
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.
A Phase III Randomized Study of Adjuvant Ipilimumab Anti-CTLA4 Therapy Versus High Dose Interferon a-2b for Resected High Risk Melanoma
Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Integrative Immune Signature of Complementary Circulating and Tumoral Biomarkers Maximizes the Predictive Power of Adjuvant Immunotherapeutic Benefits in High-risk Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Predicting immune-related thyroiditis using polygenic risk scores in patients with advanced melanoma.Journal for immunotherapy of cancer · 2026Article
- Immune Checkpoint Inhibitors in the Treatment of Advanced Melanoma in Older Patients: An Overview of Published Data.Cancers · 2025Review
- Outcome differences by sex in oncology clinical trials.Nature communications · 2024Article
- Gender oncology: recommendations and consensus of the Italian Association of Medical Oncology (AIOM).ESMO open · 2024Article
- Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance.iScience · 2023Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundWe hypothesized that a gender difference in clinical response may exist to adjuvant CTLA4 blockade with ipilimumab versus high-dose IFNα (HDI). We investigated differences in candidate immune biomarkers in the circulation and tumor microenvironment (TME). PATIENTS AND
methodsThis gender-based analysis was nested within the E1609 trial that tested adjuvant therapy with ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus HDI in high risk resected melanoma. We investigated gender differences in treatment efficacy with ipi3 and ipi10 versus HDI while adjusting for age, stage, ECOG performance (PS), ulceration, primary tumor status and lymph node number. Forest plots were created to compare overall survival (OS) and relapse free survival (RFS) between ipi and HDI. Gene expression profiling (GEP) was performed on tumors of 718 (454 male, 264 female) patients. Similarly, serum and peripheral blood mononuclear cells (PBMC) samples were tested for soluble and cellular biomarkers (N = 321 patients; 109 female and 212 male).
resultsThe subgroups of female, stage IIIC, PS = 1, ulcerated primary, in-transit metastasis demonstrated significant improvement in RFS and/or OS with ipi3 versus HDI. Female gender was significant for both OS and RFS and was further explored. In the RFS comparison, a multivariate Cox regression model including significant variables indicated a significant interaction between gender and treatment (P = 0.024). In peripheral blood, percentages of CD3+ T cells (P = 0.024) and CD3+ CD4+ helper T cells (P = 0.0001) were higher in females compared to males. Trends toward higher circulating levels of IL1β (P = 0.07) and IL6 (P = 0.06) were also found in females. Males had higher percentages of monocytes (P = 0.03) with trends toward higher percentages of regulatory T cells (T-reg). Tumor GEP analysis supported enhanced infiltration with immune cells including gammadelta T cells (P = 0.005), NK cells (P = 0.01), dendritic cells (P = 0.01), CD4+ T cells (P = 0.03), CD8+ T cells (P = 0.03) and T-reg (P = 0.008) in the tumors of females compared to males and a higher T-effector and IFNγ gene signature score (P = 0.0244).
conclusionFemale gender was associated with adjuvant CTLA4 blockade clinical benefits and female patients were more likely to have evidence of type1 immune activation within the TME and the circulation. Trial registration ClinicalTrials.gov NCT01274338. Registered 11 January 2011, https://www. CLINICALTRIALS: gov/ct2/show/NCT01274338.
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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.