High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis

  1. Cortese, Nina ORCID logo
  2. Carriero, Roberta ORCID logo
  3. Barbagallo, Marialuisa ORCID logo
  4. Putignano, Anna Rita ORCID logo
  5. Costa, Guido ORCID logo
  6. Giavazzi, Fabio ORCID logo
  7. Grizzi, Fabio ORCID logo
  8. Pasqualini, Fabio ORCID logo
  9. PEANO, CLELIA ORCID logo
  10. Basso, Gianluca ORCID logo
  11. Marchini, Sergio ORCID logo
  12. Colombo, Federico Simone ORCID logo
  13. Soldani, Cristiana ORCID logo
  14. franceschini, barbara ORCID logo
  15. di tommaso, luca ORCID logo
  16. TERRACCIANO, Luigi Maria ORCID logo
  17. Donadon, Matteo ORCID logo
  18. TORZILLI, GUIDO ORCID logo
  19. Kunderfranco, Paolo ORCID logo
  20. Mantovani, Alberto ORCID logo
  21. Marchesi, Federica ORCID logo

Download
405.pdf 10,78MB
WeightNameValue
1000 Titel
  • High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis
1000 Autor/in
  1. Cortese, Nina |
  2. Carriero, Roberta |
  3. Barbagallo, Marialuisa |
  4. Putignano, Anna Rita |
  5. Costa, Guido |
  6. Giavazzi, Fabio |
  7. Grizzi, Fabio |
  8. Pasqualini, Fabio |
  9. PEANO, CLELIA |
  10. Basso, Gianluca |
  11. Marchini, Sergio |
  12. Colombo, Federico Simone |
  13. Soldani, Cristiana |
  14. franceschini, barbara |
  15. di tommaso, luca |
  16. TERRACCIANO, Luigi Maria |
  17. Donadon, Matteo |
  18. TORZILLI, GUIDO |
  19. Kunderfranco, Paolo |
  20. Mantovani, Alberto |
  21. Marchesi, Federica |
1000 Erscheinungsjahr 2023
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2023-04-03
1000 Erschienen in
1000 Quellenangabe
  • 11(4):405-420
1000 Copyrightjahr
  • 2023
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1158/2326-6066.CIR-22-0462 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070171/ |
1000 Ergänzendes Material
  • https://aacrjournals.org/cancerimmunolres/article/11/4/405/718977/High-Resolution-Analysis-of-Mononuclear-Phagocytes#supplementary-data |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell–cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations.
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-3680-7167|https://orcid.org/0000-0001-8619-6152|https://orcid.org/0000-0003-0294-2299|https://orcid.org/0000-0002-6462-9188|https://orcid.org/0000-0003-3986-8790|https://orcid.org/0000-0003-4930-0592|https://orcid.org/0000-0003-0925-742X|https://orcid.org/0000-0003-4852-3794|https://orcid.org/0000-0001-7055-3629|https://orcid.org/0000-0002-8430-4727|https://orcid.org/0000-0003-1783-7651|https://orcid.org/0000-0003-4480-3481|https://orcid.org/0000-0001-5041-9588|https://orcid.org/0000-0001-6348-248X|https://orcid.org/0000-0002-9013-4728|https://orcid.org/0000-0002-9393-9660|https://orcid.org/0000-0003-0296-7648|https://orcid.org/0000-0001-5798-5021|https://orcid.org/0000-0001-7477-8710|https://orcid.org/0000-0001-5578-236X|https://orcid.org/0000-0002-7212-5721
1000 Label
1000 Förderer
  1. Associazione Italiana per la Ricerca sul Cancro |
  2. Ministero della Salute |
1000 Fördernummer
  1. AIRC 5x1000 21147; AIRC MFAG 22083
  2. RF-2019-12369142
1000 Förderprogramm
  1. -
  2. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Associazione Italiana per la Ricerca sul Cancro |
    1000 Förderprogramm -
    1000 Fördernummer AIRC 5x1000 21147; AIRC MFAG 22083
  2. 1000 joinedFunding-child
    1000 Förderer Ministero della Salute |
    1000 Förderprogramm -
    1000 Fördernummer RF-2019-12369142
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6453508.rdf
1000 Erstellt am 2023-08-10T13:08:57.439+0200
1000 Erstellt von 337
1000 beschreibt frl:6453508
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2023-09-04T11:36:11.839+0200
1000 Objekt bearb. Mon Sep 04 11:35:56 CEST 2023
1000 Vgl. frl:6453508
1000 Oai Id
  1. oai:frl.publisso.de:frl:6453508 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source