Language
English
Publication Date
4-10-2026
Journal
Science Immunology
DOI
10.1126/sciimmunol.aec3133
PMID
41961948
PMCID
PMC13138865
PubMedCentral® Posted Date
5-5-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Current spatial T cell receptor (TCR) profiling approaches lack the resolution needed to link clonal identity, transcriptional state, and spatial positioning of individual T cells in the tumor microenvironment. Here, we introduce a spatial TCR profiling strategy that resolves individual T cell clones together with their transcriptional states at single-cell resolution and applied the method to human head and neck squamous cell carcinoma. Presumed tumor-specific T cells were broadly dispersed throughout the tumor microenvironment, and cells of the same clone occupied distinct transcriptional states in different locations: Immune-rich regions contained more plastic or progenitor cells, whereas tumor-dense regions were enriched for exhausted states. Patients exhibited notably different spatial architectures of antitumor T cell responses, revealing variation that was not captured by high-resolution, spatially agnostic methods such as spectral flow cytometry and single-cell RNA sequencing. These results provide a blueprint for dissecting antigen-specific T cell states in human tumors and reveal how T cell states are spatially coordinated with local cues across the tumor microenvironment.
Keywords
Humans, Receptors, Antigen, T-Cell, Head and Neck Neoplasms, Single-Cell Analysis, Tumor Microenvironment, T-Lymphocytes, T-Cell Exhaustion, Squamous Cell Carcinoma of Head and Neck, Single-Cell Gene Expression Analysis
Published Open-Access
yes
Recommended Citation
McCord, Kelli A; Kan, Emerald; Hyslop, Sean; et al., "Single-Cell Tcr Mapping Reveals Spatially Coordinated T Cell States in Head and Neck Cancer" (2026). Faculty, Staff and Students Publications. 7067.
https://digitalcommons.library.tmc.edu/baylor_docs/7067