Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma
Abstract Tumor inflammation is prognostically significant in high-grade muscle-invasive bladder cancer (MIBC). However, the underlying mechanisms remain elusive. To identify inflammation-associated immune gene expression patterns, we performed transcriptomic profiling of 40 MIBC archival tumors usin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-04678-7 |
| _version_ | 1798026529836367872 |
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| author | Ekaterina Olkhov-Mitsel Anjelica Hodgson Stan K. Liu Danny Vesprini Jane Bayani John M. S. Bartlett Bin Xu Michelle R. Downes |
| author_facet | Ekaterina Olkhov-Mitsel Anjelica Hodgson Stan K. Liu Danny Vesprini Jane Bayani John M. S. Bartlett Bin Xu Michelle R. Downes |
| author_sort | Ekaterina Olkhov-Mitsel |
| collection | DOAJ |
| description | Abstract Tumor inflammation is prognostically significant in high-grade muscle-invasive bladder cancer (MIBC). However, the underlying mechanisms remain elusive. To identify inflammation-associated immune gene expression patterns, we performed transcriptomic profiling of 40 MIBC archival tumors using the NanoString nCounter Human v.1.1 PanCancer Panel. Findings were validated using the TCGA MIBC dataset. Unsupervised and supervised clustering identified a distinctive immune-related gene expression profile for inflammation, characterized by significant upregulation of 149 genes, particularly chemokines, a subset of which also had potential prognostic utility. Some of the most enriched biological processes were lymphocyte activation and proliferation, leukocyte adhesion and migration, antigen processing and presentation and cellular response to IFN-γ. Upregulation of numerous IFN-γ-inducible chemokines, class II MHC molecules and immune checkpoint genes was detected as part of the complex immune response to MIBC. Further, B-cell markers linked to tertiary lymphoid structures were upregulated, which in turn is predictive of tumor response to immunotherapy and favorable outcome. Our findings of both an overall activated immune profıle and immunosuppressive microenvironment provide novel insights into the complex immune milieu of MIBC with inflammation and supports its clinical significance for predicting prognosis and immunotherapeutic responsiveness, which warrants further investigation. This may open novel opportunities to identify mechanisms for developing new immunotherapeutic strategies. |
| first_indexed | 2024-04-11T18:37:56Z |
| format | Article |
| id | doaj.art-be1894688ab54515973ba23ef780e37b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T18:37:56Z |
| publishDate | 2022-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-be1894688ab54515973ba23ef780e37b2022-12-22T04:09:13ZengNature PortfolioScientific Reports2045-23222022-01-0112111010.1038/s41598-021-04678-7Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinomaEkaterina Olkhov-Mitsel0Anjelica Hodgson1Stan K. Liu2Danny Vesprini3Jane Bayani4John M. S. Bartlett5Bin Xu6Michelle R. Downes7Division of Anatomic Pathology, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences CentreDepartment of Pathology, Laboratory Medicine Program, University Health Network - Toronto General HospitalRadiation Oncology, Sunnybrook Health Sciences CentreRadiation Oncology, Sunnybrook Health Sciences CentreLaboratory Medicine and Pathobiology, University of TorontoDiagnostic Development, Ontario Institute for Cancer ResearchDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDivision of Anatomic Pathology, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences CentreAbstract Tumor inflammation is prognostically significant in high-grade muscle-invasive bladder cancer (MIBC). However, the underlying mechanisms remain elusive. To identify inflammation-associated immune gene expression patterns, we performed transcriptomic profiling of 40 MIBC archival tumors using the NanoString nCounter Human v.1.1 PanCancer Panel. Findings were validated using the TCGA MIBC dataset. Unsupervised and supervised clustering identified a distinctive immune-related gene expression profile for inflammation, characterized by significant upregulation of 149 genes, particularly chemokines, a subset of which also had potential prognostic utility. Some of the most enriched biological processes were lymphocyte activation and proliferation, leukocyte adhesion and migration, antigen processing and presentation and cellular response to IFN-γ. Upregulation of numerous IFN-γ-inducible chemokines, class II MHC molecules and immune checkpoint genes was detected as part of the complex immune response to MIBC. Further, B-cell markers linked to tertiary lymphoid structures were upregulated, which in turn is predictive of tumor response to immunotherapy and favorable outcome. Our findings of both an overall activated immune profıle and immunosuppressive microenvironment provide novel insights into the complex immune milieu of MIBC with inflammation and supports its clinical significance for predicting prognosis and immunotherapeutic responsiveness, which warrants further investigation. This may open novel opportunities to identify mechanisms for developing new immunotherapeutic strategies.https://doi.org/10.1038/s41598-021-04678-7 |
| spellingShingle | Ekaterina Olkhov-Mitsel Anjelica Hodgson Stan K. Liu Danny Vesprini Jane Bayani John M. S. Bartlett Bin Xu Michelle R. Downes Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma Scientific Reports |
| title | Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma |
| title_full | Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma |
| title_fullStr | Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma |
| title_full_unstemmed | Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma |
| title_short | Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma |
| title_sort | upregulation of ifnɣ mediated chemokines dominate the immune transcriptome of muscle invasive urothelial carcinoma |
| url | https://doi.org/10.1038/s41598-021-04678-7 |
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