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BRAF V600E in a preclinical model of pleomorphic Xanthoastrocytoma: Analysis of the tumor microenvironment and immune cell infiltration dynamics in vivo.
Canella, Alessandro; Nazzaro, Matthew; Artomov, Mykyta; Rao Venkata, Lakshmi Prakruthi; Thomas, Diana; Lyberger, Justin; Ukhatov, Aleksandr; Xing, Yao Lulu; Miller, Katherine; Behbehani, Gregory; Amankulor, Nduka M; Petritsch, Claudia Katharina; Rajappa, Prajwal.
Afiliación
  • Canella A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Nazzaro M; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Artomov M; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Rao Venkata LP; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Thomas D; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Lyberger J; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Ukhatov A; Department of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Xing YL; Department of Electrical Engineering. Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
  • Miller K; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Behbehani G; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Amankulor NM; Department of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Petritsch CK; Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA.
  • Rajappa P; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
Mol Ther Oncol ; 32(2): 200808, 2024 Jun 20.
Article en En | MEDLINE | ID: mdl-38784952
ABSTRACT
Low-grade glioma (LGG) is the most common brain tumor affecting pediatric patients (pLGG) and BRAF mutations constitute the most frequent genetic alterations. Within the spectrum of pLGGs, approximately 70%-80% of pediatric patients diagnosed with transforming pleomorphic xanthoastrocytoma (PXA) harbor the BRAF V600E mutation. However, the impact of glioma BRAF V600E cell regulation of tumor-infiltrating immune cells and their contribution to tumor progression remains unclear. Moreover, the efficacy of BRAF inhibitors in treating pLGGs is limited compared with their impact on BRAF-mutated melanoma. Here we report a novel immunocompetent RCAS-BRAF V600E murine glioma model. Pathological assessment indicates this model seems to be consistent with diffuse gliomas and morphological features of PXA. Our investigations revealed distinct immune cell signatures associated with increased trafficking and activation within the tumor microenvironment (TME). Intriguingly, immune system activation within the TME also generated a pronounced inflammatory response associated with dysfunctional CD8+ T cells, increased presence of immunosuppressive myeloid cells and regulatory T cells. Further, our data suggests tumor-induced inflammatory processes, such as cytokine storm. These findings suggest a complex interplay between tumor progression and the robust inflammatory response within the TME in preclinical BRAF V600E LGGs, which may significantly influence animal survival.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos