Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_BA0A2EA97728
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics.
Périodique
International journal of cancer
Auteur⸱e⸱s
Romanens L., Chaskar P., Marcone R., Ryser S., Tille J.C., Genolet R., Heimgartner-Hu K., Heimgartner K., Moore J.S., Liaudet N., Kaya G., Pittet M.J., Dietrich P.Y., Delorenzi M., Speiser D.E., Harari A., Tsantoulis P., Labidi-Galy S.I.
ISSN
1097-0215 (Electronic)
ISSN-L
0020-7136
Statut éditorial
Publié
Date de publication
01/11/2023
Peer-reviewed
Oui
Volume
153
Numéro
9
Pages
1568-1578
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Humans, Female, Breast Neoplasms/genetics, Endothelial Cells, Transcriptome, Receptors, Antigen, T-Cell, Gene Expression Profiling, Lymphocytes, Tumor-Infiltrating, Tumor Microenvironment/genetics, TCR-sequencing, clonal expansion, laser-capture microdissection, spatial TCR, spatial transcriptomics
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/06/2023 17:32
Dernière modification de la notice
10/02/2024 8:26
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