Dataset.

DataSheet_5_A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes.docx

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331353
Digital.CSIC. Repositorio Institucional del CSIC
  • Pedrosa, Leire
  • Foguet, Carles
  • Oliveres, Helena
  • Archilla, Iván
  • García de Herreros, Marta
  • Rodríguez, Adela
  • Postigo, Antonio
  • Benítez-Ribas, Daniel
  • Camps, Jordi
  • Cuatrecasas, Miriam
  • Castells, Antoni
  • Prat, Aleix
  • Thomson, Timothy M.
  • Maurel, Joan
  • Cascante, Marta
Supplementary Figure S5: Immune signatures and IMMETCOLS in 75 samples of 75 mCRC. A) heatmap of transcriptomics immune signatures in 75 mCRC stratified according to IMMETCOLS. GEP is the average expression of the genes of the GEP signature. Immunophenoscore is the aggregate of the MHC (Antigen Processing), EC (Effector cells), CP (Checkpoints and Immunomodulators) and SC (Suppressor cells) scores. B) Average immunophenogram in each IMMETCOLS cluster in the 75 mCRC. Inner circle plots each of the four Immunophenoscore components with higher values representing a more immunogenic phenotype. The outer cycle plots the expression of markers used to compute each of the immunophenoscore components., 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., Peer reviewed
 
DOI: http://hdl.handle.net/10261/331353
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331353

HANDLE: http://hdl.handle.net/10261/331353
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331353
 
Ver en: http://hdl.handle.net/10261/331353
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331353

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331353
Dataset. 2022

DATASHEET_5_A NOVEL GENE SIGNATURE UNVEILS THREE DISTINCT IMMUNE-METABOLIC REWIRING PATTERNS CONSERVED ACROSS DIVERSE TUMOR TYPES AND ASSOCIATED WITH OUTCOMES.DOCX

Digital.CSIC. Repositorio Institucional del CSIC
  • Pedrosa, Leire
  • Foguet, Carles
  • Oliveres, Helena
  • Archilla, Iván
  • García de Herreros, Marta
  • Rodríguez, Adela
  • Postigo, Antonio
  • Benítez-Ribas, Daniel
  • Camps, Jordi
  • Cuatrecasas, Miriam
  • Castells, Antoni
  • Prat, Aleix
  • Thomson, Timothy M.
  • Maurel, Joan
  • Cascante, Marta
Supplementary Figure S5: Immune signatures and IMMETCOLS in 75 samples of 75 mCRC. A) heatmap of transcriptomics immune signatures in 75 mCRC stratified according to IMMETCOLS. GEP is the average expression of the genes of the GEP signature. Immunophenoscore is the aggregate of the MHC (Antigen Processing), EC (Effector cells), CP (Checkpoints and Immunomodulators) and SC (Suppressor cells) scores. B) Average immunophenogram in each IMMETCOLS cluster in the 75 mCRC. Inner circle plots each of the four Immunophenoscore components with higher values representing a more immunogenic phenotype. The outer cycle plots the expression of markers used to compute each of the immunophenoscore components., 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., Peer reviewed




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