ArticleJournal of translational medicine2024
Sex-related differences in serum biomarker levels predict the activity and efficacy of immune checkpoint inhibitors in advanced melanoma and non-small cell lung cancer patients.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Long-term impacts of COVID-19 on systemic inflammation and control of breathing reflexes: an observational cohort study.Respiratory research · 2026Observational
- Advancing precision immuno-oncology in melanoma: the synergistic convergence of personalized neoantigen vaccines and multi-omics biomarker profiling.Frontiers in immunology · 2026Review
- A multiplexed assay by self-assembled dual-target responsive DNA hydrogels for efficacy evaluation of immunotherapy.Nature communications · 2025Article
- Soluble PD-L1 (sPD-L1) as a biomarker of durable response and survival in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitors (ICIs).Cancer immunology, immunotherapy : CII · 2025Article
- Sex-specific cytokine signatures as predictors of anti-PD1 therapy response in non-small cell lung cancer.Frontiers in immunology · 2025Article
- Prognostic value of circulating proteins at diagnosis among patients with lung cancer: a comprehensive analysis by smoking status.Translational lung cancer research · 2024Article
- Metastasis and basement membrane-related signature enhances hepatocellular carcinoma prognosis and diagnosis by integrating single-cell RNA sequencing analysis and immune microenvironment assessment.Journal of translational medicine · 2024Article
- Biomarkers of success of anti-PD-(L)1 immunotherapy for non-small cell lung cancer derived from RNA- and whole-exome sequencing: results of a prospective observational study on a cohort of 85 patients.Frontiers in immunology · 2024Observational
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundImmune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization.
methodsIn this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies.
resultsSerum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS.
conclusionsSerum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex.
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