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Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study
Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051648/ https://www.ncbi.nlm.nih.gov/pubmed/36982943 http://dx.doi.org/10.3390/ijms24065869 |
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author | Titmuss, E. Milne, K. Jones, M. R. Ng, T. Topham, J. T. Brown, S. D. Schaeffer, D. F. Kalloger, S. Wilson, D. Corbett, R. D. Williamson, L. M. Mungall, K. Mungall, A. J. Holt, R. A. Nelson, B. H. Jones, S. J. M. Laskin, J. Lim, H. J. Marra, M. A. |
author_facet | Titmuss, E. Milne, K. Jones, M. R. Ng, T. Topham, J. T. Brown, S. D. Schaeffer, D. F. Kalloger, S. Wilson, D. Corbett, R. D. Williamson, L. M. Mungall, K. Mungall, A. J. Holt, R. A. Nelson, B. H. Jones, S. J. M. Laskin, J. Lim, H. J. Marra, M. A. |
author_sort | Titmuss, E. |
collection | PubMed |
description | Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual’s cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies. |
format | Online Article Text |
id | pubmed-10051648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100516482023-03-30 Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study Titmuss, E. Milne, K. Jones, M. R. Ng, T. Topham, J. T. Brown, S. D. Schaeffer, D. F. Kalloger, S. Wilson, D. Corbett, R. D. Williamson, L. M. Mungall, K. Mungall, A. J. Holt, R. A. Nelson, B. H. Jones, S. J. M. Laskin, J. Lim, H. J. Marra, M. A. Int J Mol Sci Article Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual’s cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies. MDPI 2023-03-20 /pmc/articles/PMC10051648/ /pubmed/36982943 http://dx.doi.org/10.3390/ijms24065869 Text en © 2023 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 Titmuss, E. Milne, K. Jones, M. R. Ng, T. Topham, J. T. Brown, S. D. Schaeffer, D. F. Kalloger, S. Wilson, D. Corbett, R. D. Williamson, L. M. Mungall, K. Mungall, A. J. Holt, R. A. Nelson, B. H. Jones, S. J. M. Laskin, J. Lim, H. J. Marra, M. A. Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study |
title | Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study |
title_full | Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study |
title_fullStr | Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study |
title_full_unstemmed | Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study |
title_short | Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study |
title_sort | immune activation following irbesartan treatment in a colorectal cancer patient: a case study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051648/ https://www.ncbi.nlm.nih.gov/pubmed/36982943 http://dx.doi.org/10.3390/ijms24065869 |
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