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<p>Improved methods to identify therapeutically relevant tumor neoantigens and their cognate T cells would aid the development of precision medicines for cancer. Here, we developed Slide-GoTags, a droplet-based single-nucleus spatial transcriptomics approach that characterizes neoantigen-specific immunity by integrating targeted transcript genotyping and T cell receptor (TCR) sequencing with single-nucleus RNA sequencing from the same slice of frozen tissue. Application of Slide-GoTags to mouse and human tumors revealed colocalization of clonally expanded, neoantigen-specific T cells with tumor cells expressing their cognate neoantigen. We also identified distinct spatial immune landscapes shaped by anti-PD1 or anti-CTLA4 blockade in mouse colorectal tumors. Across human tumor types, Slide-GoTags detected TCR–neoantigen interactions through spatial proximity and identified an enrichment of interferon-driven immunogenicity niches in immunologically ‘hot’ tumors compared to ‘cold’ tumors. These niches harbored three T cell clonotypes that colocalized with genotyped neoantigens, highlighting a spatially organized antitumor immune response. Collectively, Slide-GoTags establishes a framework for in situ mapping of T cell–tumor interactions directly from individual tissue.</p>

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Single-nucleus multimodal spatial transcriptomics reveals spatial colocalization of neoantigen-expressing tumor cells and cognate T cells

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Adi Nagler,
  • Amit Sud,
  • Jack Y. Ghannam,
  • Lucas Pomerance,
  • Camila Robles-Oteiza,
  • Alexander B. Afeyan,
  • Jackson A. Weir,
  • Andrew J. C. Russell,
  • Wesley S. Lu,
  • McKayla Van Orden,
  • Andrea Sonnenholzner,
  • Giovanni J. Marrero,
  • Qiyu Gong,
  • Vipin Kumar,
  • Kun Huang,
  • Chloe Tu,
  • Emma Lin,
  • Bohoon Shim,
  • Gabriel R. De Oliveira,
  • MacLean C. Sellars,
  • Charles H. Yoon,
  • David A. Reardon,
  • Toni K. Choueiri,
  • Lars R. Olsen,
  • Sabina Signoretti,
  • Patrick A. Ott,
  • David A. Braun,
  • Giacomo Oliveira,
  • Shuqiang Li,
  • Kenneth J. Livak,
  • Nir Hacohen,
  • Fei Chen,
  • Catherine J. Wu

摘要

Improved methods to identify therapeutically relevant tumor neoantigens and their cognate T cells would aid the development of precision medicines for cancer. Here, we developed Slide-GoTags, a droplet-based single-nucleus spatial transcriptomics approach that characterizes neoantigen-specific immunity by integrating targeted transcript genotyping and T cell receptor (TCR) sequencing with single-nucleus RNA sequencing from the same slice of frozen tissue. Application of Slide-GoTags to mouse and human tumors revealed colocalization of clonally expanded, neoantigen-specific T cells with tumor cells expressing their cognate neoantigen. We also identified distinct spatial immune landscapes shaped by anti-PD1 or anti-CTLA4 blockade in mouse colorectal tumors. Across human tumor types, Slide-GoTags detected TCR–neoantigen interactions through spatial proximity and identified an enrichment of interferon-driven immunogenicity niches in immunologically ‘hot’ tumors compared to ‘cold’ tumors. These niches harbored three T cell clonotypes that colocalized with genotyped neoantigens, highlighting a spatially organized antitumor immune response. Collectively, Slide-GoTags establishes a framework for in situ mapping of T cell–tumor interactions directly from individual tissue.