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Genetically modified IL2 bone-marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment.
Canella, Alessandro; Nazzaro, Matthew; Rajendran, Sakthi; Schmitt, Claire; Haffey, Abigail; Nigita, Giovanni; Thomas, Diana; Lyberger, Justin M; Behbehani, Gregory K; Amankulor, Nduka M; Mardis, Elaine R; Cripe, Timothy P; 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.
  • Rajendran S; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Schmitt C; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Haffey A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Nigita G; Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Thomas D; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Lyberger JM; Department of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Behbehani GK; Department of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA.
  • Amankulor NM; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
  • Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus
  • Cripe TP; Center for Childhood Cancer, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
  • Rajappa P; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus
Cell Rep ; 42(8): 112891, 2023 Aug 29.
Article en En | MEDLINE | ID: mdl-37516967
Gliomas are one of the leading causes of cancer-related death in the adolescent and young adult (AYA) population. Two-thirds of AYA glioma patients are affected by low-grade gliomas (LGGs), but there are no specific treatments. Malignant progression is supported by the immunosuppressive stromal component of the tumor microenvironment (TME) exacerbated by M2 macrophages and a paucity of cytotoxic T cells. A single intravenous dose of engineered bone-marrow-derived myeloid cells that release interleukin-2 (GEMys-IL2) was used to treat mice with LGGs. Our results demonstrate that GEMys-IL2 crossed the blood-brain barrier, infiltrated the TME, and reprogrammed the immune cell composition and transcriptome. Moreover, GEMys-IL2 extended survival in an LGG immunocompetent mouse model. Here, we report the efficacy of an in vivo approach that demonstrates the potential for a cell-mediated innate immunotherapy designed to enhance the recruitment of activated effector T and natural killer cells within the glioma TME.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Rep Año: 2023 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: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos