This paper details a multimodal profiling framework developed to study T cell function in head and neck squamous cell carcinoma (HNSCC), a cancer that often resists immune checkpoint blockade. This research integrates single-cell RNA- and TCR-sequencing with spatial transcriptomics, including a novel method for spatially-resolved TCR profiling at single-cell resolution. The primary finding is that T cell function and phenotype are not solely determined by clonal identity or antigen specificity, but are dynamically shaped by their spatial location and microenvironmental cues within the tumor. Specifically, stem-like T cells are shown to cluster in immune-rich niches, while exhausted T cells are broadly dispersed in tumor-dense regions, providing critical insight into T cell organization and differentiation in solid tumors.

References:

• McCord K A, Kan E, Hyslop S, et al. Single-cell, Spatially-Resolved TCR Profiling Links T Cell Phenotype and Clonality in Human Tumors[J]. BioRxiv, 2025: 2025.08. 06.668925.