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The Personalized OncoGenomics (POG) program at BC Cancer applies whole genome and transcriptome analysis to pinpoint actionable cancer alterations. Using this approach, an advanced mismatch repair-deficient colorectal cancer patient treated with the antihypertensive drug irbesartan achieved a profound, durable response. The study tracks subsequent relapse and explores mechanisms via WGTA and multiplex immunohistochemistry on paired biopsies from the same metastatic L3 site, revealing increased immune signalling and CD8+ T-cell infiltration after treatment, with no marked genomic landscape shift before versus after. These findings suggest an irbesartan-linked activated immune response; further studies are needed to evaluate broader cancer contexts.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/immune-activation-following-irbesartan-treatment-in-a-colorectal-cancer-patient-a-case-study/382206/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/immune-activation-following-irbesartan-treatment-in-a-colorectal-cancer-patient-a-case-study/382206.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What treatment and patient context are examined in this case study?","Question",{"text":112,"@type":113},"The study follows a patient with advanced mismatch repair-deficient colorectal cancer treated with the antihypertensive drug irbesartan, after prior characterization through the POG whole genome and transcriptome program.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were changes after irbesartan assessed in the relapsed tumour?",{"text":117,"@type":113},"Paired biopsies collected before and after treatment from the same metastatic L3 spine site were analyzed using whole genome and transcriptome analysis and multiplex immunohistochemistry profiling.",{"name":119,"@type":110,"acceptedAnswer":120},"What key immunological findings are reported following irbesartan treatment?",{"text":121,"@type":113},"Analyses show increased immune signalling and infiltration of immune cells, particularly CD8+ T cells, in the relapsed tumour, supporting the idea of an activated, treatment-associated anti-tumour immune response.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},382206,1792200610,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Article  \nImmune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study  \nE. Titmuss 1, K. Milne 2, M. R. Jones 1, T. Ng 3, J. T. Topham 4, S. D. Brown 1, D. F. Schaeffer 4, S. Kalloger 3, D. Wilson 5, R. D. Corbett 1, L. M. Williamson 1, K. Mungall 1, A. J. Mungall 1, R. A. Holt 1,6, B. H. Nelson 2,6  \n,  \nS. J. M. Jones 1, J. Laskin 5, H. J. Lim 5 and M. A. Marra 1,6, *  \nCitation: 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.; et al. Immune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study. Int. J.  \nMol. Sci. 2023, 24, 5869. [https://](https://)[ ](https://)[doi.org/10.3390/ijms24065869](doi.org/10.3390/ijms24065869)  \nAcademic Editor: Carmine Stolfi  \nReceived: 18 February 2023  \nRevised: 14 March 2023  \nAccepted: 17 March 2023  \nPublished: 20 March 2023  \nCorrected: 14 November 2024  \nCopyright: © 2023 by the authors. 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada  \n2 Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada  \n3 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada  \n4 Pancreas Centre BC, Vancouver, BC V5Z 1G1, Canada  \n5 Department of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada  \n6 Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z2, Canada  \n* [Correspondence: mmarra@bcgsc.ca](Correspondence: mmarra@bcgsc.ca); Tel.: +1-604-707-5800  \nAbstract: 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.  \nKeywords: colorectal cancer; personalised medicine; irbesartan; angiotensin receptor blocker; immunotherapy; immune response; immune activation  \n1. Introduction  \nColorectal cancers (CRCs) are among the most common cancers worldwide in both men and women [1] despite the potential for early detection through population-scale screening initiatives [2] . Chemotherapy, including irinotecan and oxaliplatin, and targeted therapies, such as panitumumab and bevacizumab, are standard treatments for patients with advanced disease [3] . More recently, immune checkpoint inhibitors (ICIs) have demonstrated improved clinical outcomes for subsets of patients with CRC, such as those with deficient mismatch repair (dMMR) and high tumour mutation burden (TMB) [4] . Evidence of an immune ","cbCaigaIjqr5xFwl","https://ap.wps.com/l/cbCaigaIjqr5xFwl","pdf",2331078,13,"English","# Abstract\n# 1. Introduction\n# 2. Results\n## 2.1. Clinical Presentation","[{\"question\":\"What treatment and patient context are examined in this case study?\",\"answer\":\"The study follows a patient with advanced mismatch repair-deficient colorectal cancer treated with the antihypertensive drug irbesartan, after prior characterization through the POG whole genome and transcriptome program.\"},{\"question\":\"How were changes after irbesartan assessed in the relapsed tumour?\",\"answer\":\"Paired biopsies collected before and after treatment from the same metastatic L3 spine site were analyzed using whole genome and transcriptome analysis and multiplex immunohistochemistry profiling.\"},{\"question\":\"What key immunological findings are reported following irbesartan treatment?\",\"answer\":\"Analyses show increased immune signalling and infiltration of immune cells, particularly CD8+ T cells, in the relapsed tumour, supporting the idea of an activated, treatment-associated anti-tumour immune response.\"}]","Immune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study | PDF",1790249504,33]