Reshaping the Immune Microenvironment by Oncolytic Herpes Simplex Virus in Murine Pancreatic Ductal Adenocarcinoma.
Animals
Biomarkers
Carcinoma, Pancreatic Ductal
/ immunology
Cytokines
/ metabolism
Host Microbial Interactions
/ immunology
Humans
Lymphocytes, Tumor-Infiltrating
/ immunology
Mice
Oncolytic Virotherapy
/ methods
Oncolytic Viruses
/ genetics
Pancreatic Neoplasms
/ immunology
Simplexvirus
/ genetics
Tumor Microenvironment
/ immunology
cancer therapy
oncolytic herpes simplex virus
pancreatic ductal adenocarcinoma
single cell RNA sequencing
tumor microenvironment
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
01
05
2020
revised:
12
09
2020
accepted:
23
10
2020
pubmed:
2
11
2020
medline:
21
10
2021
entrez:
1
11
2020
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is the major type of pancreatic malignancy with very poor prognosis. Despite the promising results of immune checkpoint inhibitors (ICIs) in some solid tumors, immunotherapy is less effective for PDAC due to its immunosuppressive tumor microenvironment (TME). In this report, we established an immunocompetent syngeneic PDAC model and investigated the effect of oncolytic herpes simplex virus-1 (oHSV) on the composition of TME immune cells. The oHSV treatment significantly reduced tumor burden and prolonged the survival of tumor-bearing mice. Further, by single cell RNA sequencing (scRNA-seq) and multicolor fluorescence-activated cell sorting (FACS) analysis, we demonstrated that oHSV administration downregulated tumor-associated macrophages (TAMs), especially the anti-inflammatory macrophages, and increased the percentage of tumor-infiltrating lymphocytes, including activated cytotoxic CD8
Identifiants
pubmed: 33130310
pii: S1525-0016(20)30598-0
doi: 10.1016/j.ymthe.2020.10.027
pmc: PMC7854309
pii:
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
744-761Informations de copyright
Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
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