Spatial colocalization of neoantigen-expressing tumor cells and cognate T cells in cancer

Journal article

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.

Authors: Nagler, A; Sud, A; Ghannam, JY

• Publication status: Accepted
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Biotechnology
• Acceptance date: 2026-04-28
• EISSN: 1546-1696
• ISSN: 1087-0156
• Language: English
• Keywords: immunogenic niches; neoantigens; spatial transcriptomics; targeted genotyping; T cell receptor (TCR) sequencing; FFR