Elucidating Cellular Response to Treatment with Viral Immunotherapies in Pediatric High-grade Glioma and Medulloblastoma

Overview

Journal Transl Oncol

Specialty Oncology

Date 2024 Jan 6

PMID 38183802

Authors

Eric M Thompson

Kyung-Don Kang

Kevin Stevenson

Hengshan Zhang

Matthias Gromeier

David Ashley

Michael Brown

Gregory K Friedman

Affiliations

Soon will be listed here.

Abstract

HSV G207, a double-stranded, DNA virus, and the polio:rhinovirus chimera, PVSRIPO, a single positive-strand RNA virus, are viral immunotherapies being used to treat pediatric malignant brain tumors in clinical trials. The purpose of this work is to elucidate general response patterns and putative biomarkers of response. Multiple pediatric high-grade glioma and medulloblastoma cell lines were treated with various multiplicities of infection of G207 or PVSRIPO. There was a significant inverse correlation between expression of one HSV cellular receptor, CD111, and the lethal dose of 50% of cells (LD50) of cells treated with G207 (r = -0.985, P<0.001) but no correlation between PVSRIPO cellular receptor expression (CD155) and LD50. RNA sequencing of control cells and cells treated for 8 and 24 h revealed that there were few shared differentially expressed (DE) genes between cells treated with PVSRIPO and G207: GCLM, LANCL2, and RBM3 were enriched whilst ADAMTS1 and VEGFA were depleted. Likewise, there were few shared DE genes enriched between medulloblastoma and high-grade glioma cell lines treated with G207: GPSM2, CHECK2, SEPTIN2, EIF4G2, GCLM, GDAP1, LANCL2, and PWP1. Treatment with G207 and PVSRIPO appear to cause disparate gene enrichment and depletion suggesting disparate molecular mechanisms in malignant pediatric brain tumors.

Citing Articles

Epigenetic regulation of the human gene.

Karas K, Pastwinska J, Salkowska A, Karwaciak I, Ratajewski M Biochem Biophys Rep. 2024; 40:101827.

PMID: 39328838 PMC: 11426145. DOI: 10.1016/j.bbrep.2024.101827.

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