PMID- 33039456
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20240226
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 202
DP  - 2021 Jan
TI  - Macrophage polarization contributes to the efficacy of an oncolytic HSV-1 
      targeting human uveal melanoma in a murine xenograft model.
PG  - 108285
LID - S0014-4835(20)30543-1 [pii]
LID - 10.1016/j.exer.2020.108285 [doi]
AB  - Uveal melanoma (UM), the most common primary malignant tumor of the eye in 
      adults, is difficult-to-treat. UM has a relatively high mortality secondary to 
      distant metastasis and poor overall survival with existing therapies. The 
      oncolytic virus herpes simplex virus type-1 (HSV-1) has been approved for 
      clinical use in melanoma. This double-stranded DNA virus was suspected to 
      directly activate lysis specifically in neoplastic cells. We tested the antitumor 
      efficacy of recombinant oncolytic HSV-1-EGFP (oHSV-EGFP) in UM and characterized 
      the local and systemic antitumor innate immune response in a murine xenograft 
      model. We first determined the efficacy of the oncolytic virus in 92.1, MUM2B and 
      MP41 cell lines. In murine xenograft models, oHSV-EGFP reduced intraocular tumors 
      as well as systemic subcutaneous tumors. A significant change in cytokines was 
      observed in viral infected cells, especially a rise in IFNgamma. In vivo analyses 
      showed increased anti-tumorigenic M1 macrophages and decreased pro-tumorigenic M2 
      macrophages in peripheral blood, and intraocular and distant tumors after 
      intravitreal viral treatment. Increased infiltration of natural killer cells and 
      mature dendritic cells was also detected after viral treatment. In addition, no 
      virus was detected in major organs after the treatment. Our data support that 
      oHSV-EGFP is effective, neoplasm specific, immune active and safe, providing 
      possible clinical translatable options to treat ocular and metastatic UM.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Liu, Sisi
AU  - Liu S
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Zhang, Junwen
AU  - Zhang J
AD  - Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of 
      Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, 
      Beijing Laboratory of Biomedical Materials, Beijing, China.
FAU - Fang, Sheng
AU  - Fang S
AD  - Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of 
      Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, 
      Beijing Laboratory of Biomedical Materials, Beijing, China.
FAU - Zhang, Qing
AU  - Zhang Q
AD  - Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of 
      Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, 
      Beijing Laboratory of Biomedical Materials, Beijing, China.
FAU - Zhu, Guidong
AU  - Zhu G
AD  - Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of 
      Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, 
      Beijing Laboratory of Biomedical Materials, Beijing, China.
FAU - Tian, Yifu
AU  - Tian Y
AD  - Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of 
      Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, 
      Beijing Laboratory of Biomedical Materials, Beijing, China.
FAU - Zhao, Mingwei
AU  - Zhao M
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China. Electronic address: mingwei_zhao@outlook.com.
FAU - Liu, Fusheng
AU  - Liu F
AD  - Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of 
      Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, 
      Beijing Laboratory of Biomedical Materials, Beijing, China. Electronic address: 
      liufusheng@ccmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201009
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - Uveal melanoma
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - *Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Green Fluorescent Proteins/*physiology
MH  - Herpesvirus 1, Human/*physiology
MH  - Heterografts
MH  - Humans
MH  - Macrophage Activation/*physiology
MH  - Melanoma/metabolism/pathology/*therapy/virology
MH  - Mice, Inbred BALB C
MH  - Microscopy, Fluorescence
MH  - *Oncolytic Virotherapy
MH  - Oncolytic Viruses/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Uveal Neoplasms/metabolism/pathology/*therapy/virology
MH  - Mice
OTO - NOTNLM
OT  - HSV-1
OT  - IFNgamma
OT  - Macrophage
OT  - Metastases
OT  - Oncolytic virus
OT  - Polarization
OT  - Uveal melanoma
EDAT- 2020/10/12 06:00
MHDA- 2021/04/17 06:00
CRDT- 2020/10/11 20:23
PHST- 2020/03/22 00:00 [received]
PHST- 2020/09/04 00:00 [revised]
PHST- 2020/09/29 00:00 [accepted]
PHST- 2020/10/12 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2020/10/11 20:23 [entrez]
AID - S0014-4835(20)30543-1 [pii]
AID - 10.1016/j.exer.2020.108285 [doi]
PST - ppublish
SO  - Exp Eye Res. 2021 Jan;202:108285. doi: 10.1016/j.exer.2020.108285. Epub 2020 Oct 
      9.