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High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq

Author

Listed:
  • Jasim Kada Benotmane

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Jan Kueckelhaus

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Paulina Will

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Junyi Zhang

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Vidhya M. Ravi

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg
    Translational NeuroOncology Research Group, Medical Center—University of Freiburg)

  • Kevin Joseph

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg
    Translational NeuroOncology Research Group, Medical Center—University of Freiburg)

  • Roman Sankowski

    (Medical Center—University of Freiburg)

  • Jürgen Beck

    (Medical Center - University of Freiburg
    Freiburg University)

  • Catalina Lee-Chang

    (Northwestern University Feinberg School of Medicine)

  • Oliver Schnell

    (Medical Center - University of Freiburg
    Freiburg University
    Translational NeuroOncology Research Group, Medical Center—University of Freiburg)

  • Dieter Henrik Heiland

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg
    Northwestern University Feinberg School of Medicine)

Abstract

Spatial resolution of the T cell repertoire is essential for deciphering cancer-associated immune dysfunction. Current spatially resolved transcriptomic technologies are unable to directly annotate T cell receptors (TCR). We present spatially resolved T cell receptor sequencing (SPTCR-seq), which integrates optimized target enrichment and long-read sequencing for highly sensitive TCR sequencing. The SPTCR computational pipeline achieves yield and coverage per TCR comparable to alternative single-cell TCR technologies. Our comparison of PCR-based and SPTCR-seq methods underscores SPTCR-seq’s superior ability to reconstruct the entire TCR architecture, including V, D, J regions and the complementarity-determining region 3 (CDR3). Employing SPTCR-seq, we assess local T cell diversity and clonal expansion across spatially discrete niches. Exploration of the reciprocal interaction of the tumor microenvironmental and T cells discloses the critical involvement of NK and B cells in T cell exhaustion. Integrating spatially resolved omics and TCR sequencing provides as a robust tool for exploring T cell dysfunction in cancers and beyond.

Suggested Citation

  • Jasim Kada Benotmane & Jan Kueckelhaus & Paulina Will & Junyi Zhang & Vidhya M. Ravi & Kevin Joseph & Roman Sankowski & Jürgen Beck & Catalina Lee-Chang & Oliver Schnell & Dieter Henrik Heiland, 2023. "High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43201-6
    DOI: 10.1038/s41467-023-43201-6
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    References listed on IDEAS

    as
    1. Lung‐fei Lee & Jihai Yu, 2016. "Identification of Spatial Durbin Panel Models," Journal of Applied Econometrics, John Wiley & Sons, Ltd., vol. 31(1), pages 133-162, January.
    2. Kevin Lebrigand & Virginie Magnone & Pascal Barbry & Rainer Waldmann, 2020. "High throughput error corrected Nanopore single cell transcriptome sequencing," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    3. Vidhya M. Ravi & Nicolas Neidert & Paulina Will & Kevin Joseph & Julian P. Maier & Jan Kückelhaus & Lea Vollmer & Jonathan M. Goeldner & Simon P. Behringer & Florian Scherer & Melanie Boerries & Marie, 2022. "T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Christoph Kuppe & Mahmoud M. Ibrahim & Jennifer Kranz & Xiaoting Zhang & Susanne Ziegler & Javier Perales-Patón & Jitske Jansen & Katharina C. Reimer & James R. Smith & Ross Dobie & John R. Wilson-Kan, 2021. "Decoding myofibroblast origins in human kidney fibrosis," Nature, Nature, vol. 589(7841), pages 281-286, January.
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    1. Jan Kueckelhaus & Simon Frerich & Jasim Kada-Benotmane & Christina Koupourtidou & Jovica Ninkovic & Martin Dichgans & Juergen Beck & Oliver Schnell & Dieter Henrik Heiland, 2024. "Inferring histology-associated gene expression gradients in spatial transcriptomic studies," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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