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

Jasim Benotmane, Jan Kueckelhaus, Paulina Will, Junyi Zhang, Vidhya Ravi, Kevin Joseph, Roman Sankowski, Jürgen Beck, Catalina Lee-Chang, Oliver Schnell, Dieter Heiland (2023) High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq Nat Commun (IF: 18.1) 14(1) 7432

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.© 2023. The Author(s).

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654577
http://www.ncbi.nlm.nih.gov/pubmed/37973846
http://dx.doi.org/10.1038/s41467-023-43201-6

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