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April 5, 2026Cancer Research0 citations

Abstract 817: Spatial characterization, of T-cell receptors at subcellular resolution using in situ sequencing-by-synthesis and spatial protein detection on the same tissue section.

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HMHansueli MeyerRPRobert PinardRHRyan Hindman

Key Points

  • The aim is to develop a method for analyzing T-cell receptors within their spatial context in tumor tissues.
  • Combined in situ sequencing-by-synthesis with high-plex protein detection on the same FFPE section.
  • Utilized rolling circle amplified RNA detection probes and conjugated antibodies.
  • Conducted detailed analysis of TCRs using FFPE tissue sections of five to ten µm thickness.
  • Identified high diversity of clonotypes and assigned them to T-cell subtypes.
  • Generated clonotype maps that visualize T-cell populations in tissue.
  • Co-localized alpha and beta chain receptors within same cells and mapped immune cell protein markers.

Abstract

Abstract Abstract: Analyzing the tumor microenvironment (TME) and its immune context based on protein and RNA expression, alongside RNA sequencing, offers a powerful approach to understand tumor biology, predict treatment response, and guide the development of personalized therapies. It provides a more comprehensive understanding of tumor biology and the interplay between genetic alterations, cellular environment, and immune response. Currently, commercially available spatial transcriptomics methods require cDNA barcoding on tissue and ex situ cDNA sequencing on a separate instrument which limits the ability to directly sequence known or unknown regions in situ, such as T-cell or B-cell receptor (TCR/BCR) complementarity determining regions. This limitation can impact the detailed analysis of immune responses within tissue. Advances in technology are needed to enable direct in situ sequencing for more comprehensive insights. Here, we present a novel approach combining in situ sequencing-by-synthesis with high-plex protein detection (30+), H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 817.

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Cite This Study

Meyer et al. (2026) studied this question.

synapsesocial.com/papers/69d1fceba79560c99a0a2a26https://doi.org/10.1158/1538-7445.am2026-817
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