Universidad Peruana Cayetano Heredia

A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes

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dc.contributor.author Pedrosa, L.
dc.contributor.author Foguet, C.
dc.contributor.author Oliveres, H.
dc.contributor.author Archilla, I.
dc.contributor.author de Herreros, M.G.
dc.contributor.author Rodríguez, Adela
dc.contributor.author Postigo, A.
dc.contributor.author Benítez-Ribas, D.
dc.contributor.author Camps, J.
dc.contributor.author Cuatrecasas, M.
dc.contributor.author Castells, A.
dc.contributor.author Prat, A.
dc.contributor.author Thomson Okatsu, Timothy M.
dc.contributor.author Maurel, J.
dc.contributor.author Cascante, M.
dc.date.accessioned 2022-10-12T18:25:57Z
dc.date.available 2022-10-12T18:25:57Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12366
dc.description.abstract Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/β-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches. en_US
dc.language.iso eng
dc.publisher Frontiers Media
dc.relation.ispartofseries Frontiers in Immunology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject biomarker en_US
dc.subject immunotherapy en_US
dc.subject precision medicine en_US
dc.subject metabolism en_US
dc.subject immune checkpoint-based therapy en_US
dc.title A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3389/fimmu.2022.926304
dc.relation.issn 1664-3224


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