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

Jasim Kada Benotmane, Jan Kueckelhaus, Paulina Will, Junyi Zhang, Vidhya M. Ravi, Kevin Joseph, Roman Sankowski, Jürgen Beck, Catalina Lee-Chang, Oliver Schnell and Dieter Henrik Heiland ()
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Jasim Kada Benotmane: Medical Center - University of Freiburg
Jan Kueckelhaus: Medical Center - University of Freiburg
Paulina Will: Medical Center - University of Freiburg
Junyi Zhang: Medical Center - University of Freiburg
Vidhya M. Ravi: Medical Center - University of Freiburg
Kevin Joseph: Medical Center - University of Freiburg
Roman Sankowski: Medical Center—University of Freiburg
Jürgen Beck: Medical Center - University of Freiburg
Catalina Lee-Chang: Northwestern University Feinberg School of Medicine
Oliver Schnell: Medical Center - University of Freiburg
Dieter Henrik Heiland: Medical Center - University of Freiburg

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43201-6

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DOI: 10.1038/s41467-023-43201-6

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