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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_BA0A2EA97728
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics.
Journal
International journal of cancer
Author(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
Publication state
Published
Issued date
01/11/2023
Peer-reviewed
Oui
Volume
153
Number
9
Pages
1568-1578
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
15/06/2023 16:32
Last modification date
10/02/2024 7:26
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