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Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer |
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| Author: | Elomaa, Hanna1,2; Ahtiainen, Maarit3; Väyrynen, Sara A.4; |
| Organizations: |
1Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland 2Department of Education and Research, Hospital Nova of Central Finland, Well Being Services County of Central Finland, Jyväskylä, Finland 3Department of Pathology, Hospital Nova of Central Finland, Well Being Services County of Central Finland, Jyväskylä, Finland
4Department of Internal Medicine, Oulu University Hospital, Oulu, Finland
5Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 6Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 7Broad Institute of MIT and Harvard, Cambridge, MA, USA 8Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA 9Institute of Molecular Cell Biology, Agency of Science, Technology and Research (A*STAR), Singapore, Singapore 10Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland 11Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland 12Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland 13Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland 14Applied Tumor Genomics, Research Program Unit, University of Helsinki, Helsinki, Finland 15Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 7.5 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe20230825108391 |
| Language: | English |
| Published: |
Springer Nature,
2023
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| Publish Date: | 2023-08-25 |
| Description: |
AbstractBackground: The CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint interaction may promote cancer progression, but the expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised. Methods: We used a custom 9-plex immunohistochemistry assay to quantify the expression patterns of PD-L1 and PD-1 in macrophages, T cells, and tumour cells in 910 colorectal cancer patients. We evaluated cancer-specific mortality according to immune cell subset densities using multivariable Cox regression models. Results: Compared to PD-L1⁻ macrophages, PD-L1⁺ macrophages were more likely M1-polarised than M2-polarised and located closer to tumour cells. PD-L1⁺ macrophage density in the invasive margin associated with longer cancer-specific survival [Ptrend= 0.0004, HR for the highest vs. lowest quartile, 0.52; 95% CI: 0.34–0.78]. T cell densities associated with longer cancer-specific survival regardless of PD-1 expression (Ptrend < 0.005 for both PD-1⁺ and PD-1⁻ subsets). Higher densities of PD-1⁺ T cell/PD-L1⁺ macrophage clusters associated with longer cancer-specific survival (Ptrend < 0.005). Conclusions: PD-L1⁺ macrophages show distinct polarisation profiles (more M1-like), spatial features (greater co-localisation with tumour cells and PD-1⁺ T cells), and associations with favourable clinical outcome. Our comprehensive multimarker assessment could enhance the understanding of immune checkpoints in the tumour microenvironment and promote the development of improved immunotherapies. see all
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| Series: |
British journal of cancer |
| ISSN: | 0007-0920 |
| ISSN-E: | 1532-1827 |
| ISSN-L: | 0007-0920 |
| Volume: | 128 |
| Issue: | 11 |
| Pages: | 2104 - 2115 |
| DOI: | 10.1038/s41416-023-02238-6 |
| OADOI: | https://oadoi.org/10.1038/s41416-023-02238-6 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3122 Cancers |
| Subjects: | |
| Funding: |
This study was funded by Cancer Foundation Finland (59-5619 to J.P. Väyrynen) and Emil Aaltonen Foundation (220022K to H. Elomaa). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Open Access funding provided by University of Oulu including Oulu University Hospital. |
| Copyright information: |
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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https://creativecommons.org/licenses/by/4.0/ |