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

Article Article scientifique Article Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics eng 2023-06-12 2023-06-12 author Romanens Lou 0000-0002-6454-0503 Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland. 798685 author Chaskar Prasad Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland.,Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland. 913442 author Marcone Rachel 0000-0002-5711-8435 SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. author Ryser Stephan Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland. 81605 Expérimentation animale (EXPAM) author Tille Jean-Christophe 0000-0002-2255-5918 Department of Diagnosis, Division of Clinical Pathology, Hôpitaux Universitaires de Genève, Genève, Switzerland. 87627 author Genolet Raphael Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research, University of Lausanne, Swiss Cancer Center Leman, Lausanne, Switzerland. author Hu Ketty Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland. 812691 author Heimgartner Killian Olivier Marie Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland. 934648 author Moore Jonathan Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland. 949979 author Liaudet Nicolas 0000-0002-0749-5857 Bioimaging Core Facility, Faculty of Medicine, University of Geneva, Genève, Switzerland. 862067 Services communs de la faculté de médecine (SCMU) author Kaya Guerkan Department of Diagnosis, Division of Clinical Pathology, Hôpitaux Universitaires de Genève, Genève, Switzerland.,Department of Medicine, Division of Dermatology, Hôpitaux Universitaires de Genève, Genève, Switzerland. 26603 Département de médecine (DEMED) author Pittet Mikaël 0000-0002-2060-4691 Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland.,Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Genève, Switzerland.,Ludwig Institute for Cancer Research, Lausanne, Switzerland.,AGORA Cancer Center, Lausanne, Switzerland. 917678 Département de pathologie et immunologie (PATIM) author Dietrich Pierre-Yves 0000-0002-7375-6939 Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland.,Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland. 96532 Décanat et administration de la faculté de médecine (ADMED) author Delorenzi Mauro 0000-0001-7631-3263 SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.,Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research, University of Lausanne, Swiss Cancer Center Leman, Lausanne, Switzerland. author Speiser Daniel E Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research, University of Lausanne, Swiss Cancer Center Leman, Lausanne, Switzerland. author Harari Alexandre Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research, University of Lausanne, Swiss Cancer Center Leman, Lausanne, Switzerland.,AGORA Cancer Center, Lausanne, Switzerland. author Tsantoulis Petros 0000-0003-3613-6682 Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland.,Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland. 861166 Département de médecine (DEMED) author Labidi-Galy Sana Intidhar 0000-0002-0824-3475 Faculty of Medicine, Department of Medicine and Center of Translational Research in Onco-Hematology, University of Geneva, Swiss Cancer Center Leman, Genève, Switzerland.,Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland. 817058 Département de médecine (DEMED) 10.1002/ijc.34620 37306359 0020-7136 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. TCR-sequencing Clonal expansion Laser-capture microdissection Spatial TCR Spatial transcriptomics Dewey 616.07 Dewey 616 Swiss National Science Foundation Impact of oophorectomy on breast cancers in BRCA1 mutation carriers 173959 CH Careers 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 false 1388 Cancers de la femme 1040 579 Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) 922 391 Métastases du foie 657 478 Rôle du CD44 809 1336 Comprendre et manipuler le système immunitaire pour lutter contre le cancer 1024 27 Immunothérapie des cancers 42 https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-8760 https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-11903?accession=E-MTAB-11903 https://ega-archive.org/studies/EGAS00001007125 International journal of cancer 2fde3ed9-99f0-4a40-b309-08e55649ec9f Article (Published version) Public Intl Journal of Cancer - 2023 - Rom1.pdf 12364902 application/pdf CC BY 3de13adb5bec457048535eb598f10999dd79b72cb01b1ea2132ebb9de63c7035 a91f2ab0-501c-488f-9b63-b28097d7a11e Supplemental data Public ijc34620-sup-0001-supinfo.pdf 56111714 application/pdf CC BY c8b0762ec2fc2846bc27cd788b886ad54152c258ff0c1e1b4615cd15217d3049 65334e6a-5c36-417a-bdad-e5d09eed00b1 Supplemental data Public ijc34620-sup-0002-tables(1).xls 241152 application/vnd.ms-excel CC BY 5d5c310fa16aee1e3fb5fc7bb19e8e5fdfecc84ca92d64b07a264cdc27d5cca2 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine

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Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics	International journal of cancer			2023	516	106

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