Nature Biotechnology | 空间多组学解码新抗原-T 细胞原位互作：为 mRNA 肿瘤疫苗精准设计奠定核心技术框架

TL;DR - A Nature Biotechnology study introduces Slide-GoTags, a spatial single-nucleus multi-omics method that jointly maps gene expression, neoantigen mutations, T-cell receptors, and cellular locations. It could improve mRNA cancer-vaccine design by identifying neoantigens that trigger genuine in situ T-cell responses rather than relying mainly on computational predictions.

• Slide-GoTags integrates spatial transcriptomics, targeted mutation genotyping, and full-length TCR sequencing on the same frozen tissue section.
• In mouse tumors and samples from nine patients across four cancer types, neoantigen-expressing tumor cells spatially colocalized with cognate T-cell clones.
• The study identifies IFN-driven “immunogenic niches” as major sites of antigen-specific T-cell recruitment, clonal expansion, activation, and exhaustion.
• Strong HLA-binding neoantigens attracted more CD8+ T cells but were also associated with greater T-cell exhaustion, supporting vaccine combinations with checkpoint blockade.