High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq
Benotmane JK, Kueckelhaus J, Will P, Zhang J, Ravi VM, Joseph K, Sankowski R, Beck J, Lee-Chang C, Schnell O, Heiland DH (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 14
Article Number: 7432
Journal Issue: 1
DOI: 10.1038/s41467-023-43201-6
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.
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Germany (DE)
United States (USA) (US)How to cite
APA:
Benotmane, J.K., Kueckelhaus, J., Will, P., Zhang, J., Ravi, V.M., Joseph, K.,... Heiland, D.H. (2023). High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-43201-6
MLA:
Benotmane, Jasim Kada, et al. "High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq." Nature Communications 14.1 (2023).
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