Journal article
Single-nucleus multimodal spatial transcriptomics reveals spatial colocalization of neoantigen-expressing tumor cells and cognate T cells
- Abstract:
- Unique nucleotide sequences in somatic mutations and T cell receptors (TCR) provide molecular barcodes by which diverse tumor clones and T cells, respectively, can be distinguished. To define the spatial organization of tumor neoantigen-specific T cells relative to their tumor targets and other cellular components of the tumor microenvironment (TME), we developed Slide-GoTags, a droplet-based spatial transcriptomics platform that integrates targeted transcript genotyping and TCR sequencing with single nucleus RNA-sequencing. Application of Slide-GoTagsto murine and human tumors revealed colocalization of clonally expanded, neoantigen-specific T cells with tumor cells expressing their cognate neoantigen. T cell functional state, local immune niche composition and clonotype expansion and avidity were linked to neoantigen proximity, highlighting a spatially organized anti-tumor immune response. Collectively, Slide-GoTags establishes a framework for in situ mapping of T cell-tumor interactions directly from patient tissue.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 65.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s41587-026-03194-1
Authors
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 227000/Z/23/Z
- Publisher:
- Springer Nature
- Journal:
- Nature Biotechnology More from this journal
- Publication date:
- 2026-07-22
- Acceptance date:
- 2026-05-26
- DOI:
- EISSN:
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1546-1696
- ISSN:
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1087-0156
- Language:
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English
- Keywords:
- Pubs id:
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2412243
- Local pid:
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pubs:2412243
- Deposit date:
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2026-04-28
- ARK identifier:
Terms of use
- Copyright holder:
- Nagler et al
- Copyright date:
- 2026
- Rights statement:
- © 2026, The Author(s), under exclusive licence to Springer Nature America, Inc.
- Notes:
- The author accepted manuscript (AAM) of this paper has been made available under the University of Oxford's Open Access Publications Policy, and a CC BY public copyright licence has been applied.
- Licence:
- CC Attribution (CC BY)
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