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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Shared Science Publishers OG
2022
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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. |
format | Online Article Text |
id | pubmed-9442149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Shared Science Publishers OG |
record_format | MEDLINE/PubMed |
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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