ORCID Profile
0000-0003-0901-1286
Current Organisations
University of Queensland
,
University of California, San Diego
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Publisher: The American Association of Immunologists
Date: 05-2023
DOI: 10.4049/JIMMUNOL.210.SUPP.66.03
Abstract: Immune checkpoint blockade (ICB) therapy has been revolutionary in its ability to treat advanced malignancies. Yet many patients receiving ICB develop Immune related adverse events (IRAEs), a leading cause for patients to discontinue treatment. Analyzing patients who develop IRAEs can help advance our knowledge of the molecular drivers of these poorly understood off target toxicities. Our recent study of plasma from patients undergoing ipilimumab (anti-CTLA4) or pembrolizumab (anti-PD1) therapy for melanoma, lung cancer or other solid tumors was assessed using high-resolution liquid chromatography-tandem mass spectrometry. We uncovered a novel protective mechanism related to a class of circulating bio-active lipids that suppress ICB-related IRAEs. Significant reduction of bio-active lipids in circulation was associated with increased ICB-mediated IRAEs. Mouse-models (both DSS-colitis and humanized models) were used to show that supplementation with these lipids ameliorated colonic inflammation without impacting ICB-driven tumor regression. We also uncovered a significant correlation between increasing neutrophil counts and decreased bioactive lipids in circulation. These results uncover a previously unidentified regulatory mechanism whereby the identified lipids in circulation specifically suppress deleterious inflammation during ICB therapy, while preserving anti-tumor immunity, suggesting that supplementation of bio-active lipids can be developed as a new therapeutic strategy to improve clinical outcomes in cancer immunotherapy. Supported by grants from NIH (R01CA256133-02)
Publisher: MDPI AG
Date: 27-10-2020
Abstract: Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 in iduals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) 0.05 in VITAL200, validated (p-values 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 06-07-2021
DOI: 10.1186/S13059-021-02413-Z
Abstract: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target. This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.
Publisher: Fortune Journals
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 24-08-2020
Publisher: Springer Science and Business Media LLC
Date: 29-05-2013
DOI: 10.1038/NG0613-713A
Publisher: European Respiratory Society (ERS)
Date: 17-06-2021
Location: United States of America
No related grants have been discovered for Julio Fernandez Banet.