دورية أكاديمية
Integrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer
| العنوان: | Integrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer |
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| المؤلفون: | Desbois, Mélanie, Udyavar, Akshata R., Ryner, Lisa, Kozlowski, Cleopatra, Guan, Yinghui, Dürrbaum, Milena, Lu, Shan, Fortin, Jean-Philippe, Koeppen, Hartmut, Ziai, James, Chang, Ching-Wei, Keerthivasan, Shilpa, Plante, Marie, Bourgon, Richard, Bais, Carlos, Hegde, Priti, Daemen, Anneleen, Turley, Shannon, Wang, Yulei |
| المساهمون: | Genentech |
| المصدر: | Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what controls the spatial distribution of T cells in the tumour microenvironment is not well understood. Here we couple digital pathology and transcriptome analysis on a large ovarian tumour cohort and develop a machine learning approach to molecularly classify and characterize tumour-immune phenotypes. Our study identifies two important hallmarks characterizing T cell excluded tumours: 1) loss of antigen presentation on tumour cells and 2) upregulation of TGFβ and activated stroma. Furthermore, we identify TGFβ as an important mediator of T cell exclusion. TGFβ reduces MHC-I expression in ovarian cancer cells in vitro. TGFβ also activates fibroblasts and induces extracellular matrix production as a potential physical barrier to hinder T cell infiltration. Our findings indicate that targeting TGFβ might be a promising strategy to overcome T cell exclusion and improve clinical benefits of cancer immunotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-020-19408-2 |
| الإتاحة: | https://doi.org/10.1038/s41467-020-19408-2Test https://www.nature.com/articles/s41467-020-19408-2.pdfTest https://www.nature.com/articles/s41467-020-19408-2Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.23E4923C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-19408-2 |
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