{
  "abstract": "Background Pediatric brain tumors (PBTs), including medulloblastoma and H3K27M-mutant diffuse midline gliomas, remain the most lethal childhood cancers and exhibit limited responsiveness to current immunotherapies. As a young investigator committed to developing precision immunotherapy strategies for pediatric patients, I aim to characterize the immune microenvironment of PBTs and identify mechanisms of immune evasion, with a focus on PD-1-mediated T cell dysfunction.Methods In this investigator-initiated study, fresh tumor tissue and matched peripheral blood mononuclear cells (PBMCs) were prospectively obtained from pediatric patients undergoing neurosurgery at Cohen Children’s Medical Center. Patient-derived tumor organoids (PDTOs) were generated and subjected to multiplex flow cytometry and histological validation. Immunogenic potential was assessed by stimulating PDTOs with IFN-γ and analyzing MHC-I and PD-L1 expression. Archival tumor samples were profiled using multiplex immunofluorescence to spatially map immune cell phenotypes and tumor heterogeneity.Results Preliminary analyses revealed that tumor-infiltrating CD8 + T cells exhibited features of exhaustion, including high PD-1 expression. PDTOs preserved key histopathological and immunological features of the parental tumors and responded to IFN-γ with upregulation of MHC-I and PD-L1 in a subset of samples. Multiplex imaging of archival specimens revealed heterogeneous immune cell infiltration and potential suppressive microenvironments across tumor subtypes.Conclusions This work establishes a patient-centric platform to model tumor-immune interactions in pediatric brain tumors and highlights PD-1-associated T cell exhaustion as a mechanism of immune evasion. As a next step, co-culture assays with autologous immune cells are underway to functionally assess immune responses and test checkpoint blockade. These efforts aim to inform rational immunotherapy development and offer new hope for children with high-risk, treatment-refractory brain tumors.",
  "authors": [
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA",
        "Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA"
      ],
      "name": "Meri Rogava"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Zarina Brune"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Anjali Rachelkar"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Rachel Pruitt"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Jung Park"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Amanda Huang"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Amanda Beneat"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Morris Edelman"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Mark Atlas"
    },
    {
      "affiliations": [
        "Cancer Research Center of Lyon, Leon, France"
      ],
      "name": "Erika Cosset"
    },
    {
      "affiliations": [
        "Ccmc Northwell, New York, NY, USA"
      ],
      "name": "Steven Schneider"
    },
    {
      "affiliations": [
        "Northwell Health, New York, NY, USA"
      ],
      "name": "Betsy Barnes"
    }
  ],
  "title": "362 Dissecting immune evasion in pediatric brain tumors through organoid models and multiplex immune profiling",
  "uid": "0062a0f2-b1c3-591b-8570-edacabb56bfc"
}