Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC
Abstract B cells have emerged as central players in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). However, although there is clear evidence for their involvement in cancer immunity, scanty data exist on the characterization of B cell phenotypes, bioenergetic profiles and po...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-024-02209-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594988840517632 |
|---|---|
| author | Domenico Lo Tartaro Beatrice Aramini Valentina Masciale Nikolaos Paschalidis Francesco Demetrio Lofaro Anita Neroni Rebecca Borella Elena Santacroce Alin Liviu Ciobanu Anna Valeria Samarelli Federica Boraldi Daniela Quaglino Alessandra Dubini Michele Gaudio Gloria Manzotti Francesca Reggiani Federica Torricelli Alessia Ciarrocchi Antonino Neri Federica Bertolini Massimo Dominici Pier Luigi Filosso Franco Stella Lara Gibellini Sara De Biasi Andrea Cossarizza |
| author_facet | Domenico Lo Tartaro Beatrice Aramini Valentina Masciale Nikolaos Paschalidis Francesco Demetrio Lofaro Anita Neroni Rebecca Borella Elena Santacroce Alin Liviu Ciobanu Anna Valeria Samarelli Federica Boraldi Daniela Quaglino Alessandra Dubini Michele Gaudio Gloria Manzotti Francesca Reggiani Federica Torricelli Alessia Ciarrocchi Antonino Neri Federica Bertolini Massimo Dominici Pier Luigi Filosso Franco Stella Lara Gibellini Sara De Biasi Andrea Cossarizza |
| author_sort | Domenico Lo Tartaro |
| collection | DOAJ |
| description | Abstract B cells have emerged as central players in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). However, although there is clear evidence for their involvement in cancer immunity, scanty data exist on the characterization of B cell phenotypes, bioenergetic profiles and possible interactions with T cells in the context of NSCLC. In this study, using polychromatic flow cytometry, mass cytometry, and spatial transcriptomics we explored the intricate landscape of B cell phenotypes, bioenergetics, and their interaction with T cells in NSCLC. Our analysis revealed that TME contains diverse B cell clusters, including VISTA+ Bregs, with distinct metabolic and functional profiles. Target liquid chromatography-tandem mass spectrometry confirmed the expression of VISTA on B cells. VISTA+ Bregs displayed high metabolic demand and were able to produce different cytokines, including interleukin (IL)-10, transforming growth factor (TGF)-β, IL-6, tumor necrosis factor (TNF), and granulocyte–macrophage colony-stimulating factor (GM-CSF). Spatial analysis showed colocalization of B cells with CD4+/CD8+ T lymphocytes in TME. The computational analysis of intercellular communications that links ligands to target genes, performed by NicheNet, predicted B-T interactions via VISTA-PSGL-1 axis. Colocalization analyses revealed that PSGL-1 T cells and VISTA+ B cells are adjacent in the TME. Notably, tumor infiltrating CD8+ T cells expressing PSGL-1 exhibited enhanced metabolism and cytotoxicity. In NSCLC patients, prediction analysis performed by PENCIL revealed the presence of an association between PSGL-1+CD8+ T cells and VISTA+ Bregs with lung recurrence. Our findings suggest a potential interaction between Bregs and T cells through the VISTA-PSGL-1 axis, that could influence NSCLC recurrence. |
| format | Article |
| id | doaj-art-9435e8144204444b9cbc82b85cef0a7b |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-9435e8144204444b9cbc82b85cef0a7b2025-01-19T12:12:34ZengBMCMolecular Cancer1476-45982025-01-0124112810.1186/s12943-024-02209-2Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLCDomenico Lo Tartaro0Beatrice Aramini1Valentina Masciale2Nikolaos Paschalidis3Francesco Demetrio Lofaro4Anita Neroni5Rebecca Borella6Elena Santacroce7Alin Liviu Ciobanu8Anna Valeria Samarelli9Federica Boraldi10Daniela Quaglino11Alessandra Dubini12Michele Gaudio13Gloria Manzotti14Francesca Reggiani15Federica Torricelli16Alessia Ciarrocchi17Antonino Neri18Federica Bertolini19Massimo Dominici20Pier Luigi Filosso21Franco Stella22Lara Gibellini23Sara De Biasi24Andrea Cossarizza25Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDivision of Thoracic Surgery, Department of Medical and Surgical Sciences – DIMEC, University of Bologna, G.B. Morgagni -L. Pierantoni HospitalDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaBiomedical Research Foundation, Academy of AthensDepartment of Life Sciences, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Life Sciences, University of Modena and Reggio EmiliaDepartment of Life Sciences, University of Modena and Reggio EmiliaDivision of Pathology, G.B. Morgagni—L. Pierantoni HospitalDivision of Pathology, G.B. Morgagni—L. Pierantoni HospitalLaboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaLaboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaLaboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaLaboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaLaboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDivision of Thoracic Surgery, Department of Medical and Surgical Sciences – DIMEC, University of Bologna, G.B. Morgagni -L. Pierantoni HospitalDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio EmiliaAbstract B cells have emerged as central players in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). However, although there is clear evidence for their involvement in cancer immunity, scanty data exist on the characterization of B cell phenotypes, bioenergetic profiles and possible interactions with T cells in the context of NSCLC. In this study, using polychromatic flow cytometry, mass cytometry, and spatial transcriptomics we explored the intricate landscape of B cell phenotypes, bioenergetics, and their interaction with T cells in NSCLC. Our analysis revealed that TME contains diverse B cell clusters, including VISTA+ Bregs, with distinct metabolic and functional profiles. Target liquid chromatography-tandem mass spectrometry confirmed the expression of VISTA on B cells. VISTA+ Bregs displayed high metabolic demand and were able to produce different cytokines, including interleukin (IL)-10, transforming growth factor (TGF)-β, IL-6, tumor necrosis factor (TNF), and granulocyte–macrophage colony-stimulating factor (GM-CSF). Spatial analysis showed colocalization of B cells with CD4+/CD8+ T lymphocytes in TME. The computational analysis of intercellular communications that links ligands to target genes, performed by NicheNet, predicted B-T interactions via VISTA-PSGL-1 axis. Colocalization analyses revealed that PSGL-1 T cells and VISTA+ B cells are adjacent in the TME. Notably, tumor infiltrating CD8+ T cells expressing PSGL-1 exhibited enhanced metabolism and cytotoxicity. In NSCLC patients, prediction analysis performed by PENCIL revealed the presence of an association between PSGL-1+CD8+ T cells and VISTA+ Bregs with lung recurrence. Our findings suggest a potential interaction between Bregs and T cells through the VISTA-PSGL-1 axis, that could influence NSCLC recurrence.https://doi.org/10.1186/s12943-024-02209-2BregsNSCLCRecurrencePredictionPSGL-1VISTA |
| spellingShingle | Domenico Lo Tartaro Beatrice Aramini Valentina Masciale Nikolaos Paschalidis Francesco Demetrio Lofaro Anita Neroni Rebecca Borella Elena Santacroce Alin Liviu Ciobanu Anna Valeria Samarelli Federica Boraldi Daniela Quaglino Alessandra Dubini Michele Gaudio Gloria Manzotti Francesca Reggiani Federica Torricelli Alessia Ciarrocchi Antonino Neri Federica Bertolini Massimo Dominici Pier Luigi Filosso Franco Stella Lara Gibellini Sara De Biasi Andrea Cossarizza Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC Molecular Cancer Bregs NSCLC Recurrence Prediction PSGL-1 VISTA |
| title | Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC |
| title_full | Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC |
| title_fullStr | Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC |
| title_full_unstemmed | Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC |
| title_short | Metabolically activated and highly polyfunctional intratumoral VISTA+ regulatory B cells are associated with tumor recurrence in early-stage NSCLC |
| title_sort | metabolically activated and highly polyfunctional intratumoral vista regulatory b cells are associated with tumor recurrence in early stage nsclc |
| topic | Bregs NSCLC Recurrence Prediction PSGL-1 VISTA |
| url | https://doi.org/10.1186/s12943-024-02209-2 |
| work_keys_str_mv | AT domenicolotartaro metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT beatricearamini metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT valentinamasciale metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT nikolaospaschalidis metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT francescodemetriolofaro metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT anitaneroni metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT rebeccaborella metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT elenasantacroce metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT alinliviuciobanu metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT annavaleriasamarelli metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT federicaboraldi metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT danielaquaglino metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT alessandradubini metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT michelegaudio metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT gloriamanzotti metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT francescareggiani metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT federicatorricelli metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT alessiaciarrocchi metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT antoninoneri metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT federicabertolini metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT massimodominici metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT pierluigifilosso metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT francostella metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT laragibellini metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT saradebiasi metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc AT andreacossarizza metabolicallyactivatedandhighlypolyfunctionalintratumoralvistaregulatorybcellsareassociatedwithtumorrecurrenceinearlystagensclc |