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Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression

Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would antagonize the anti-tumor immune response and lead...

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Autores principales: Walsh, Michael J, Ali, Lestat R, Lenehan, Patrick, Kureshi, Courtney T, Kureshi, Rakeeb, Dougan, Michael, Knipe, David M, Dougan, Stephanie K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349916/
https://www.ncbi.nlm.nih.gov/pubmed/37461742
http://dx.doi.org/10.1093/immadv/ltad011
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author Walsh, Michael J
Ali, Lestat R
Lenehan, Patrick
Kureshi, Courtney T
Kureshi, Rakeeb
Dougan, Michael
Knipe, David M
Dougan, Stephanie K
author_facet Walsh, Michael J
Ali, Lestat R
Lenehan, Patrick
Kureshi, Courtney T
Kureshi, Rakeeb
Dougan, Michael
Knipe, David M
Dougan, Stephanie K
author_sort Walsh, Michael J
collection PubMed
description Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would antagonize the anti-tumor immune response and lead to tumor outgrowth. We previously demonstrated that continuous treatment with a non-replicating herpes simplex virus 1 expressing interleukin (IL)-12 induces a state of cancer immune equilibrium highly dependent on interferon-γ. We profiled the IL-12 virotherapy-induced immune equilibrium in murine melanoma, identifying blockade of innate inflammatory cytokines, tumor necrosis factor alpha (TNFα), IL-1β, or IL-6 as possible synergistic interventions. Antibody depletions of each of these cytokines enhanced survival in mice treated with IL-12 virotherapy and helped to overcome equilibrium in some tumors. Single-cell RNA-sequencing demonstrated that blockade of inflammatory cytokines resulted in downregulation of overlapping inflammatory pathways in macrophages, shifting immune equilibrium towards tumor clearance, and raising the possibility that TNFα blockade could synergize with existing cancer immunotherapies.
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spelling pubmed-103499162023-07-17 Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression Walsh, Michael J Ali, Lestat R Lenehan, Patrick Kureshi, Courtney T Kureshi, Rakeeb Dougan, Michael Knipe, David M Dougan, Stephanie K Immunother Adv Research Article Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would antagonize the anti-tumor immune response and lead to tumor outgrowth. We previously demonstrated that continuous treatment with a non-replicating herpes simplex virus 1 expressing interleukin (IL)-12 induces a state of cancer immune equilibrium highly dependent on interferon-γ. We profiled the IL-12 virotherapy-induced immune equilibrium in murine melanoma, identifying blockade of innate inflammatory cytokines, tumor necrosis factor alpha (TNFα), IL-1β, or IL-6 as possible synergistic interventions. Antibody depletions of each of these cytokines enhanced survival in mice treated with IL-12 virotherapy and helped to overcome equilibrium in some tumors. Single-cell RNA-sequencing demonstrated that blockade of inflammatory cytokines resulted in downregulation of overlapping inflammatory pathways in macrophages, shifting immune equilibrium towards tumor clearance, and raising the possibility that TNFα blockade could synergize with existing cancer immunotherapies. Oxford University Press 2023-07-03 /pmc/articles/PMC10349916/ /pubmed/37461742 http://dx.doi.org/10.1093/immadv/ltad011 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Walsh, Michael J
Ali, Lestat R
Lenehan, Patrick
Kureshi, Courtney T
Kureshi, Rakeeb
Dougan, Michael
Knipe, David M
Dougan, Stephanie K
Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
title Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
title_full Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
title_fullStr Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
title_full_unstemmed Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
title_short Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
title_sort blockade of innate inflammatory cytokines tnfα, il-1β, or il-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349916/
https://www.ncbi.nlm.nih.gov/pubmed/37461742
http://dx.doi.org/10.1093/immadv/ltad011
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