ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Circulating Immune Bioenergetic, Metabolic, and Genetic Signatures Predict Melanoma Patients' Response to Anti-PD-1 Immune Checkpoint Blockade.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Review
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- Identification of potential hub biomarkers for gastric high-grade intraepithelial neoplasia early diagnosis: evidence from gene expression profiles and pathological characters.Translational cancer research · 2026Article
- Autofluorescence lifetime imaging resolves cell heterogeneity within peripheral blood mononuclear cells.bioRxiv : the preprint server for biology · 2026Article
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- ctDNA and immune biomarker testing for molecular residual disease surveillance and immune stratification in cancer.Frontiers in medicine · 2026Review
- Profiling Serum Oxylipin Metabolites Across Melanoma Subtypes and Immunotherapy Responders.Metabolites · 2025Article
- Salivary metabolic profile landscape for gastric cancer screening: a metabolomic approach.Cancer cell international · 2025Article
- Integrating pathology genomics and single-cell genomics to identify lactate metabolism-related prognostic features and therapeutic strategies for melanoma.Apoptosis : an international journal on programmed cell death · 2025Article
- Single-Cell Transcriptomics Unravels Growth Factor Erv1-Like Mediated Ferroptosis as a Key Driver of Intestinal Epithelial Dysfunction in Ulcerative Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intra-tumoral hypoxia promotes CD8Immunity · 2025Article
- Immunometabolism: The role of gut-derived microbial metabolites in optimising immune response during checkpoint inhibitor therapy.Clinical and translational medicine · 2025Review
- Metabolic reprogramming in melanoma therapy.Cell death discovery · 2025Review
- Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma.Scientific reports · 2025Article
- Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies.Cancers · 2025Review
- Metabolomic signatures in liquid biopsy are associated with overall survival in metastatic melanoma patients treated with immune checkpoint inhibitor therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Shared genes and relevant potential molecular linkages between COVID-19 and chronic thromboembolic pulmonary hypertension (CTEPH).Journal of thrombosis and thrombolysis · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
purposeImmunotherapy with checkpoint inhibitors is improving the outcomes of several cancers. However, only a subset of patients respond. Therefore, predictive biomarkers are critically needed to guide treatment decisions and develop approaches to the treatment of therapeutic resistance. EXPERIMENTAL
designWe compared bioenergetics of circulating immune cells and metabolomic profiles of plasma obtained at baseline from patients with melanoma treated with anti-PD-1 therapy. We also performed single-cell RNA sequencing (scRNAseq) to correlate transcriptional changes associated with metabolic changes observed in peripheral blood mononuclear cells (PBMC) and patient plasma.
resultsPretreatment PBMC from responders had a higher reserve respiratory capacity and higher basal glycolytic activity compared with nonresponders. Metabolomic analysis revealed that responder and nonresponder patient samples cluster differently, suggesting differences in metabolic signatures at baseline. Differential levels of specific lipid, amino acid, and glycolytic pathway metabolites were observed by response. Further, scRNAseq analysis revealed upregulation of T-cell genes regulating glycolysis. Our analysis showed that SLC2A14 (Glut-14; a glucose transporter) was the most significant gene upregulated in responder patients' T-cell population. Flow cytometry analysis confirmed significantly elevated cell surface expression of the Glut-14 in CD3+, CD8+, and CD4+ circulating populations in responder patients. Moreover, LDHC was also upregulated in the responder population.
conclusionsOur results suggest a glycolytic signature characterizes checkpoint inhibitor responders; consistently, both ECAR and lactate-to-pyruvate ratio were significantly associated with overall survival. Together, these findings support the use of blood bioenergetics and metabolomics as predictive biomarkers of patient response to immune checkpoint inhibitor therapy.
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