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IFNγ is a central node of cancer immune equilibrium

Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune system. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. Using a non-replicating HSV-1 vector expressing...

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Autores principales: Walsh, Michael J., Stump, Courtney T., Kureshi, Rakeeb, Lenehan, Patrick, Ali, Lestat R., Dougan, Michael, Knipe, David M., Dougan, Stephanie K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214249/
https://www.ncbi.nlm.nih.gov/pubmed/36881506
http://dx.doi.org/10.1016/j.celrep.2023.112219
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author Walsh, Michael J.
Stump, Courtney T.
Kureshi, Rakeeb
Lenehan, Patrick
Ali, Lestat R.
Dougan, Michael
Knipe, David M.
Dougan, Stephanie K.
author_facet Walsh, Michael J.
Stump, Courtney T.
Kureshi, Rakeeb
Lenehan, Patrick
Ali, Lestat R.
Dougan, Michael
Knipe, David M.
Dougan, Stephanie K.
author_sort Walsh, Michael J.
collection PubMed
description Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune system. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. Using a non-replicating HSV-1 vector expressing interleukin-12 (d106S-IL12), we developed a mouse model of therapy-induced immune equilibrium, a phenomenon previously seen only in humans. This immune equilibrium was centrally reliant on interferon-γ (IFNγ). CD8(+) T cell direct recognition of MHC class I, perforin/granzyme-mediated cytotoxicity, and extrinsic death receptor signaling such as Fas/FasL were all individually dispensable for equilibrium. IFNγ was critically important and played redundant roles in host and tumor cells such that IFNγ sensing in either compartment was sufficient for immune equilibrium. We propose that these redundant mechanisms of action are integrated by IFNγ to protect from oncogenic or chronic viral threats and establish IFNγ as a central node in therapy-induced immune equilibrium.
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spelling pubmed-102142492023-05-26 IFNγ is a central node of cancer immune equilibrium Walsh, Michael J. Stump, Courtney T. Kureshi, Rakeeb Lenehan, Patrick Ali, Lestat R. Dougan, Michael Knipe, David M. Dougan, Stephanie K. Cell Rep Article Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune system. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. Using a non-replicating HSV-1 vector expressing interleukin-12 (d106S-IL12), we developed a mouse model of therapy-induced immune equilibrium, a phenomenon previously seen only in humans. This immune equilibrium was centrally reliant on interferon-γ (IFNγ). CD8(+) T cell direct recognition of MHC class I, perforin/granzyme-mediated cytotoxicity, and extrinsic death receptor signaling such as Fas/FasL were all individually dispensable for equilibrium. IFNγ was critically important and played redundant roles in host and tumor cells such that IFNγ sensing in either compartment was sufficient for immune equilibrium. We propose that these redundant mechanisms of action are integrated by IFNγ to protect from oncogenic or chronic viral threats and establish IFNγ as a central node in therapy-induced immune equilibrium. 2023-03-28 2023-03-06 /pmc/articles/PMC10214249/ /pubmed/36881506 http://dx.doi.org/10.1016/j.celrep.2023.112219 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Walsh, Michael J.
Stump, Courtney T.
Kureshi, Rakeeb
Lenehan, Patrick
Ali, Lestat R.
Dougan, Michael
Knipe, David M.
Dougan, Stephanie K.
IFNγ is a central node of cancer immune equilibrium
title IFNγ is a central node of cancer immune equilibrium
title_full IFNγ is a central node of cancer immune equilibrium
title_fullStr IFNγ is a central node of cancer immune equilibrium
title_full_unstemmed IFNγ is a central node of cancer immune equilibrium
title_short IFNγ is a central node of cancer immune equilibrium
title_sort ifnγ is a central node of cancer immune equilibrium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214249/
https://www.ncbi.nlm.nih.gov/pubmed/36881506
http://dx.doi.org/10.1016/j.celrep.2023.112219
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