Biology subjects

D'Apuzzo, M.

Publications and source records attributed to D'Apuzzo, M..

2 recordsLinked to original sources

bioRxiv2026

A long-term organotypic slice culture model of patient high-grade glioma preserving tumor heterogeneity and architecture, and specificity of CAR T cell targeting

ABSTRACT Background: High grade glioma (HGG), encompassing IDH-wildtype glioblastoma (CNS WHO grade 4), diffuse midline glioma (CNS WHO grade 4), oligodendroglioma (IDH-mutant and 1p/19q-codeleted) CNS WHO grade 3, together with IDH-mutant astrocytoma of CNS grade 3 and grade 4, represents the most lethal group of adult diffuse gliomas. Despite significant efforts, obtaining improvements in patient survival has been limited, in part, by difficulties in comprehensive ex vivo modeling of the complexities of HGG. Although organotypic slice cultures and other platforms have shown promise, existing models often fail to capture the intrinsic cellular heterogeneity, microenvironment, and architecture of HGG, restricting investigations into their fundamental biology as well as design of novel therapeutics. Methods: We developed a patient-derived HGG organotypic slice culture (GOSC) platform demonstrating long-term preservation of intrinsic tumor characteristics. Vibratome-sectioned slices were cultured in defined medium under conditions approximating those in situ: reduced oxygen (4%), low glucose (2.5 mM), and no added growth factors. The characteristics of GOSCs after 28 days in culture, including expression of immunotherapy targets, were compared to parental tumors using histological staining, immunofluorescence, multiplexed PhenoCycler (CODEX) imaging, bulk RNA-seq expression profiling, and CAR T cell killing assays. Results: GOSCs preserved the histopathology, cell heterogeneity, tumor microenvironment, and tissue architecture of their parental tumors throughout at least 28 days in culture. Importantly, GOSCs retained parental patterns of immunotherapy target expression, and CAR T cells co-cultured with GOSCs demonstrated target-specific killing consistent with parental tumors. Conclusions: This ex vivo GOSC platform offers long-term preservation of the cellular and structural properties of parental HGG tumors, thereby providing a robust tool for extended preclinical studies, and facilitating development and evaluation of advanced tumor-targeting strategies.

cancer biology↗

bioRxiv2026

Patient-Derived Glioma Models Preserve Tumor Heterogeneity and Identify Stearoyl-CoA Desaturase1 (SCD1) as a Candidate Biomarker for Precision Immunotherapy

Background: Pediatric and adult brain tumors, including glioblastoma, astrocytoma, ependymoma, and medulloblastoma, remain associated with poor prognosis despite advances in surgery, radiation, and chemotherapy. Therapeutic resistance, tumor heterogeneity, and treatment-related toxicity highlight the need for clinically relevant models that enable precision medicine and immunotherapy development. Methods: Freshly dispersed tumors (FDTs), low-passage patient-derived brain tumor (PBT) spheroid lines, and matched patient-derived xenograft (PDX) models were established from patients with primary brain tumors. Models were characterized using single-cell and bulk RNA sequencing, whole-exome sequencing, multiparameter flow cytometry, and immunohistochemistry. PBTs were compared with matched FDTs to evaluate model fidelity. Results: PBT lines were established in approximately 68% of cases and retained key patient-specific genomic alterations, including IDH1, MGMT, TP53, and PTEN, with expression of therapeutically relevant targets, including IL13R2, EGFR, HER2, WNT1, JAK1/2, and NOTCH1-4. Gene expression profiles of PBTs closely correlated with matched FDTs (R = 0.38, P = 0.0038). PBT and PDX models preserved intratumoral heterogeneity and non-clonal populations, enabling identification of therapy-resistant subclones during in vitro selection. Molecular analyses identified Stearoyl-CoA Desaturase1 (SCD1) as an overexpressed biomarker across glioma PBTs and matched patient tumors. Ingenuity Pathway Analysis identified SCD1 as an upstream regulator of EGFR-, TP53-, and CYCS-associated signaling networks implicated in tumor progression and immune suppression. Conclusions: Clinically relevant PBT and matched PDX models recapitulate molecular, transcriptional, and histopathological characteristics of primary brain tumors. These platforms provide tools for biomarker discovery, therapeutic testing, and precision immunotherapy development, while identifying SCD1 as a biomarker and therapeutic target in glioma.

cancer biology↗