A spatial view of tumor neoantigen recognition
Nature Biotechnology, Published online: 22 July 2026; doi:10.1038/s41587-026-03203-3 The cell-by-cell interactions between neoantigen-expressing tumor cells and tumor-specific T cells remained largely unexplored. A single-cell spatial transcriptomics framework enables mapping of neoantigen-expressing tumor cells and tumor-infiltrating T cells, as well as T cell receptor sequencing. This approach…
Recent research reveals a spatial view of tumor neoantigen recognition, offering insights into the immune interactions within the tumor microenvironment. A team led by Nagler et al. employed single-nucleus multimodal spatial transcriptomics to map the locations of neoantigen-expressing tumor cells and tumor-infiltrating T cells. This technique allowed for the identification of distinct immune niches within the tumor, each with unique properties influencing tumor-specific responses.
The study builds upon prior work by Gubin et al. (2015), which established a framework for personalized cancer immunotherapy targeting tumor neoantigens. Additionally, Sarkizova et al. (2020) contributed to the field by providing a large dataset of human leukocyte antigen (HLA) class I peptides, essential for predicting epitope presentation. Simoni et al. (2018) discovered that bystander CD8+ T cells are abundant and phenotypically distinct in human tumor infiltrates, highlighting the complexity of anti-tumor responses.
The advancement in spatial transcriptomics, as detailed by Rosenberg and Restifo (2015) and Russell et al. (2024), enables the simultaneous analysis of multiple data types. Techniques like Slide-tags (Russell et al., 2024) facilitate single-nucleus barcoding, enhancing the ability to study cellular interactions in their spatial context. Together, these studies collectively advance our understanding of tumor neoantigen recognition and its implications for personalized cancer immunotherapy.
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