دورية أكاديمية
Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics
| العنوان: | Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics |
|---|---|
| المؤلفون: | Romanens, Lou, Chaskar, Prasad, Marcone, Rachel, Ryser, Stephan, Tille, Jean-Christophe, Genolet, Raphael, Hu, Ketty, Heimgartner, Killian Olivier Marie, Moore, Jonathan, Liaudet, Nicolas, Kaya, Guerkan, Pittet, Mikaël, Dietrich, Pierre-Yves, Delorenzi, Mauro, Speiser, Daniel E, Harari, Alexandre, Tsantoulis, Petros, Labidi-Galy, Sana Intidhar |
| المصدر: | ISSN: 0020-7136 ; International journal of cancer, (2023. |
| سنة النشر: | 2023 |
| المجموعة: | Université de Genève: Archive ouverte UNIGE |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/616.07, info:eu-repo/classification/ddc/616, TCR-sequencing, Clonal expansion, Laser-capture microdissection, Spatial TCR, Spatial transcriptomics |
| الوصف: | The spatial distribution of tumor-infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing tumors. Here, we present ST-FFPE, a spatial transcriptomics method for the analysis of formalin-fixed paraffin-embedded samples, which opens the possibility of interrogating archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser-capture, and can be used to study the cellular composition of tumor microenvironment. Focusing on triple-negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra-epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra-epithelial T and B cells were consistently less diverse and more clonal than those of stromal T and B cells. T-cell receptor (TCR) sequencing confirmed a reduced diversity and higher clonality of intra-epithelial T cells relative to the corresponding stromal T cells. Analysis of the top 10 dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra-epithelial T cells. Hyperexpanded clonotypes were more abundant among intra-epithelial than stromal T cells. These findings validate the ST-FFPE method and suggest an accumulation of antigen-specific T cells within tumor core. Because ST-FFPE is applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/37306359; info:eu-repo/semantics/dataset/url/https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-8760Test; info:eu-repo/semantics/dataset/url/https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-11903?accession=E-MTAB-11903Test; info:eu-repo/semantics/dataset/url/https://ega-archive.org/studies/EGAS00001007125Test; https://archive-ouverte.unige.ch/unige:170611Test; unige:170611 |
| الإتاحة: | https://doi.org/10.1002/ijc.34620Test https://archive-ouverte.unige.ch/unige:170611Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.129184EC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |