Oncolytic virus-driven immune remodeling revealed in mouse medulloblastomas at single cell resolution

Jack Hedberg; Adam Studebaker; Luke Smith; Chun-Yu Chen; Jesse J. Westfall; Maren Cam; Amy Gross; Ilse Hernandez-Aguirre; Alexia Martin; Doyeon Kim; Ravi Dhital; Yeaseul Kim; Ryan D. Roberts; Timothy P. Cripe; Elaine R. Mardis; Kevin A. Cassady; Jeffrey Leonard; Katherine E. Miller

Molecular Therapy: Oncolytics (Sep 2023)

Oncolytic virus-driven immune remodeling revealed in mouse medulloblastomas at single cell resolution

Jack Hedberg,
Adam Studebaker,
Luke Smith,
Chun-Yu Chen,
Jesse J. Westfall,
Maren Cam,
Amy Gross,
Ilse Hernandez-Aguirre,
Alexia Martin,
Doyeon Kim,
Ravi Dhital,
Yeaseul Kim,
Ryan D. Roberts,
Timothy P. Cripe,
Elaine R. Mardis,
Kevin A. Cassady,
Jeffrey Leonard,
Katherine E. Miller

Affiliations

Jack Hedberg: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Adam Studebaker: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Luke Smith: Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Chun-Yu Chen: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Jesse J. Westfall: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Maren Cam: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Amy Gross: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Ilse Hernandez-Aguirre: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Alexia Martin: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Doyeon Kim: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Ravi Dhital: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Yeaseul Kim: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
Ryan D. Roberts: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA; Division of Hematology/Oncology/BMT, Nationwide Children’s Hospital, Columbus, OH 43205, USA
Timothy P. Cripe: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA; Division of Hematology/Oncology/BMT, Nationwide Children’s Hospital, Columbus, OH 43205, USA
Elaine R. Mardis: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Kevin A. Cassady: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Jeffrey Leonard: The Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA; Department of Neurosurgery, Nationwide Children’s Hospital, Columbus, OH 43205, USA
Katherine E. Miller: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA; Corresponding author: Katherine E. Miller, The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, USA.

Journal volume & issue: Vol. 30
pp. 39 – 55

Abstract

Read online

Oncolytic viruses, modified for tumor-restricted infection, are a promising cancer immunotherapeutic, yet much remains to be understood about factors driving their activity and outcome in the tumor microenvironment. Here, we report that oncolytic herpes simplex virus C134, previously found to exert T cell-dependent efficacy in mouse models of glioblastoma, exerts T cell-independent efficacy in mouse models of medulloblastoma, indicating this oncolytic virus uses different mechanisms in different tumors. We investigated C134’s behavior in mouse medulloblastomas, using single cell RNA sequencing to map C134-induced gene expression changes across cell types, timepoints, and medulloblastoma subgroup models at whole-transcriptome resolution. Our work details substantial oncolytic virus-induced transcriptional remodeling of medulloblastoma-infiltrating immune cells, 10 subpopulations of monocytes and macrophages collectively demonstrating M1-like responses to C134, and suggests C134 be investigated as a potential new therapy for medulloblastoma.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

About the journal

Abstract

Keywords