COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation

Cytotoxic therapies, such as chemotherapy and radiotherapy, are mainstays of cancer treatment for both early and unresectable, advanced disease. In addition to debulking the tumour mass through direct killing of proliferating tumour cells, these treatments can promote tumour control via immune-stimu...

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Autores principales: Bell, Charlotte R., Zelenay, Santiago
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442149/
https://www.ncbi.nlm.nih.gov/pubmed/36120509
http://dx.doi.org/10.15698/cst2022.09.271
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author Bell, Charlotte R.
Zelenay, Santiago
author_facet Bell, Charlotte R.
Zelenay, Santiago
author_sort Bell, Charlotte R.
collection PubMed
description Cytotoxic therapies, such as chemotherapy and radiotherapy, are mainstays of cancer treatment for both early and unresectable, advanced disease. In addition to debulking the tumour mass through direct killing of proliferating tumour cells, these treatments can promote tumour control via immune-stimulating effects. Nonetheless, chemoresistance and tumour relapse remain huge clinical problems, suggesting that induction of anti-cancer immunity post-cytotoxic therapy is often weak, not durable and/or overcome by immune evasive mechanisms. In our recent study (Nat Commun 13:2063), we demonstrate that cancer cell-intrinsic activation of the cyclooxygenase (COX)-2/prostaglandin E(2) (PGE(2)) pathway post-chemotherapy treatment is a prevalent phenomenon which profoundly alters the inflammatory properties of the treated cancer cells. Of particular translational relevance, our findings support a model whereby upregulation of COX-2 expression and activity post-chemotherapy impairs the efficacy of the combination of PD-1 blockade and chemotherapy. Accordingly, pharmacological inhibition of COX-2 with celecoxib, an anti-inflammatory drug already used clinically, unleashed tumour control in preclinical models when given alongside chemoimmunotherapy combinations.
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spelling pubmed-94421492022-09-16 COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation Bell, Charlotte R. Zelenay, Santiago Cell Stress Microreview Cytotoxic therapies, such as chemotherapy and radiotherapy, are mainstays of cancer treatment for both early and unresectable, advanced disease. In addition to debulking the tumour mass through direct killing of proliferating tumour cells, these treatments can promote tumour control via immune-stimulating effects. Nonetheless, chemoresistance and tumour relapse remain huge clinical problems, suggesting that induction of anti-cancer immunity post-cytotoxic therapy is often weak, not durable and/or overcome by immune evasive mechanisms. In our recent study (Nat Commun 13:2063), we demonstrate that cancer cell-intrinsic activation of the cyclooxygenase (COX)-2/prostaglandin E(2) (PGE(2)) pathway post-chemotherapy treatment is a prevalent phenomenon which profoundly alters the inflammatory properties of the treated cancer cells. Of particular translational relevance, our findings support a model whereby upregulation of COX-2 expression and activity post-chemotherapy impairs the efficacy of the combination of PD-1 blockade and chemotherapy. Accordingly, pharmacological inhibition of COX-2 with celecoxib, an anti-inflammatory drug already used clinically, unleashed tumour control in preclinical models when given alongside chemoimmunotherapy combinations. Shared Science Publishers OG 2022-08-16 /pmc/articles/PMC9442149/ /pubmed/36120509 http://dx.doi.org/10.15698/cst2022.09.271 Text en Copyright: © 2022 Bell and Zelenay. https://creativecommons.org/licenses/by/4.0/This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Microreview
Bell, Charlotte R.
Zelenay, Santiago
COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
title COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
title_full COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
title_fullStr COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
title_full_unstemmed COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
title_short COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
title_sort cox-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
topic Microreview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442149/
https://www.ncbi.nlm.nih.gov/pubmed/36120509
http://dx.doi.org/10.15698/cst2022.09.271
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