{
  "abstract": "Background Immunotherapy has transformed cancer treatment, highlighting the importance of effective antitumor immunity to fight cancer. However, its success in pediatric cancer remains limited, underscoring the urgent need to identify new immunotherapeutic targets. In this study, we explored the clinical relevance of B cells and tertiary lymphoid structures (TLS) in neuroblastoma (NB), a pediatric tumor with a heterogeneous immune landscape.Methods We analyzed 87 treatment-naïve NB specimens, spanning both localized and metastatic disease previously characterized for T-cell and dendritic cell (DC) infiltration. B cells were detected by immunohistochemistry, and plasma cells were quantified using multiple immunofluorescence. Spatial organization and functional status of immune cells within TLSs were assessed by imaging mass cytometry using a 29-antibody panel. In parallel, gene expression profiles were obtained through NanoString PanCancer Immune Profiling and further validated using publicly available bulk and single-cell RNA-sequencing data from untreated and treated NB samples. These transcriptomic datasets were used to support protein-level findings and to identify prognostic gene signatures.Results B-cell infiltration in NB tumors strongly correlated with the presence of T cells and DCs at both protein and transcriptomic levels, and was associated with improved prognosis. Similar to other solid tumors, B cells in NB were either scattered throughout the tumor or organized into TLSs of varying maturity. Spatial proteomic and transcriptomic analyses revealed that localized tumors often contain mature TLSs, with functional B cells able to antigen presentation and immunoglobulin expression, alongside high cytotoxic T cells. In contrast, metastatic tumors primarily exhibited immature TLSs, with evidence of B-cell and T-cell dysfunction. Importantly, we identified gene signatures associated with B cells and TLSs that not only predicted survival in NB but were also prognostic in multiple adult cancers.Conclusions Our findings highlight a central role for B cells and TLSs in shaping the immune microenvironment of NB. Their presence and maturation status are linked to clinical outcome, suggesting their potential as prognostic biomarkers and targets for novel immunotherapeutic strategies in pediatric oncology.",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy",
        "Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy"
      ],
      "name": "Ombretta Melaiu"
    },
    {
      "affiliations": [
        "Data Science for Health, Fondazione Bruno Kessler Research Center, Trento, Italy"
      ],
      "name": "Marco Chierici"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Paula Gragera"
    },
    {
      "affiliations": [
        "Data Science for Health, Fondazione Bruno Kessler Research Center, Trento, Italy"
      ],
      "name": "Nicolò Lazzaro"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Lucia L Petrilli"
    },
    {
      "affiliations": [
        "Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands"
      ],
      "name": "Judith Wienke"
    },
    {
      "affiliations": [
        "Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands"
      ],
      "name": "Francisca J Bergsma"
    },
    {
      "affiliations": [
        "Division of Pediatric Oncology and Pediatric Surgery, Department of Women's and Children’s Health, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Bronte Manouk Verhoeven"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Cristiano De Stefanis"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Valentina D’Oria"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Maria C Benedetti"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy"
      ],
      "name": "Giovanni Barillari"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Rita Alaggio"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Maria Antonietta De Ioris"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Maria Vinci"
    },
    {
      "affiliations": [
        "Division of Pediatric Oncology and Pediatric Surgery, Department of Women's and Children’s Health, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Ninib Baryawno"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Rita Carsetti"
    },
    {
      "affiliations": [
        "Data Science for Health, Fondazione Bruno Kessler Research Center, Trento, Italy",
        "Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy"
      ],
      "name": "Giuseppe Jurman"
    },
    {
      "affiliations": [
        "Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands"
      ],
      "name": "Jan J Molenaar"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy",
        "Department of Life Sciences and Public Health, Catholic University of the Sacred Heart, Rome, Italy"
      ],
      "name": "Franco Locatelli"
    },
    {
      "affiliations": [
        "Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy"
      ],
      "name": "Doriana Fruci"
    }
  ],
  "title": "Mapping B cells and the immune landscape of tertiary lymphoid structures reveals their clinical impact in neuroblastoma",
  "uid": "a2595275-230a-588b-ae2a-7c275345025c"
}