Nat Biotechnol | 单核多模态空间转录组技术解析肿瘤新抗原与同源T细胞原位空间互作

TL;DR - A Nature Biotechnology study introduces Slide-GoTags, a single-nucleus multimodal spatial transcriptomics platform that maps neoantigen-expressing tumor cells and cognate T cells in situ. It could help identify therapeutic TCRs and spatial biomarkers of immunotherapy response.

• Slide-GoTags jointly captures nuclear transcriptomes, somatic mutations, full-length TCR CDR3 sequences, and spatial barcodes from one frozen tissue section.
• Mouse and human studies found that cognate T cells selectively colocalize with neoantigen-bearing tumor cells, with proximity linked to T-cell activation and exhaustion.
• Across nine samples from four cancer types, the study identified interferon-driven immunogenic niches enriched for expanded T-cell clones and neoantigen–TCR pairings.
• Current limitations include frozen-tissue dependence, reduced detection of low-abundance transcripts, small clinical cohorts, and the need to functionally validate inferred TCR specificity.