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Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides. In this study, we explore the combination of a ferroptosis activator with an oncolytic vaccinia virus in tumor models. Erastin induced cell death in hepatoma, colon, and ovarian...

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Autores principales: Liu, Weilin, Chen, Hongqi, Zhu, Zhi, Liu, Zuqiang, Ma, Congrong, Lee, Yong J., Bartlett, David L., Guo, Zong-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219720/
https://www.ncbi.nlm.nih.gov/pubmed/35740445
http://dx.doi.org/10.3390/biomedicines10061425
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author Liu, Weilin
Chen, Hongqi
Zhu, Zhi
Liu, Zuqiang
Ma, Congrong
Lee, Yong J.
Bartlett, David L.
Guo, Zong-Sheng
author_facet Liu, Weilin
Chen, Hongqi
Zhu, Zhi
Liu, Zuqiang
Ma, Congrong
Lee, Yong J.
Bartlett, David L.
Guo, Zong-Sheng
author_sort Liu, Weilin
collection PubMed
description Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides. In this study, we explore the combination of a ferroptosis activator with an oncolytic vaccinia virus in tumor models. Erastin induced cell death in hepatoma, colon, and ovarian cancer cells, but not in melanoma cancer cells. Erastin, not the oncolytic vaccinia virus (OVV), induced the expression of key marker genes for ferroptosis in cancer cells. In hepatocellular carcinoma and colon cancer models, either erastin or OVV inhibited tumor growth, but a combination of the two yielded the best therapeutic effects, as indicated by inhibited tumor growth or regression and longer host survival. Immunological analyses indicate that erastin alone had little or no effect on systemic immunity or local immunity in the tumor. However, when combined with OV, erastin enhanced the number of activated dendritic cells and the activity of tumor-infiltrating T lymphocytes as indicated by an increase in IFN-γ(+)CD8(+) and PD-1(+)CD8(+) T cells. These results demonstrate that erastin can exert cytotoxicity on cancer cells via ferroptosis, but has little effect on immune activity by itself. However, when combined with an OVV, erastin promoted antitumoral immunity and efficacy by increasing the number of activated dendritic cells and promoting the activities of tumor specific CD8(+) T cells in the tumor.
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spelling pubmed-92197202022-06-24 Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy Liu, Weilin Chen, Hongqi Zhu, Zhi Liu, Zuqiang Ma, Congrong Lee, Yong J. Bartlett, David L. Guo, Zong-Sheng Biomedicines Article Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides. In this study, we explore the combination of a ferroptosis activator with an oncolytic vaccinia virus in tumor models. Erastin induced cell death in hepatoma, colon, and ovarian cancer cells, but not in melanoma cancer cells. Erastin, not the oncolytic vaccinia virus (OVV), induced the expression of key marker genes for ferroptosis in cancer cells. In hepatocellular carcinoma and colon cancer models, either erastin or OVV inhibited tumor growth, but a combination of the two yielded the best therapeutic effects, as indicated by inhibited tumor growth or regression and longer host survival. Immunological analyses indicate that erastin alone had little or no effect on systemic immunity or local immunity in the tumor. However, when combined with OV, erastin enhanced the number of activated dendritic cells and the activity of tumor-infiltrating T lymphocytes as indicated by an increase in IFN-γ(+)CD8(+) and PD-1(+)CD8(+) T cells. These results demonstrate that erastin can exert cytotoxicity on cancer cells via ferroptosis, but has little effect on immune activity by itself. However, when combined with an OVV, erastin promoted antitumoral immunity and efficacy by increasing the number of activated dendritic cells and promoting the activities of tumor specific CD8(+) T cells in the tumor. MDPI 2022-06-15 /pmc/articles/PMC9219720/ /pubmed/35740445 http://dx.doi.org/10.3390/biomedicines10061425 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Weilin
Chen, Hongqi
Zhu, Zhi
Liu, Zuqiang
Ma, Congrong
Lee, Yong J.
Bartlett, David L.
Guo, Zong-Sheng
Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy
title Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy
title_full Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy
title_fullStr Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy
title_full_unstemmed Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy
title_short Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy
title_sort ferroptosis inducer improves the efficacy of oncolytic virus-mediated cancer immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219720/
https://www.ncbi.nlm.nih.gov/pubmed/35740445
http://dx.doi.org/10.3390/biomedicines10061425
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