Fig. 5: The TProlif_Tox gene signature is found across both primary tumor and metastatic nodal HNSCC with clonotype overlap, suggesting shared tumor antigen targets.
a Schematic of biospecimens and tissue analyses for patient P120. b Exomic and transcriptional mutational analyses demonstrates conserved coding mutations across tumor, involved node, and patient-derived malignant line. c Co-culture between a patient-derived malignant line and autologous extracted TILs demonstrates concentration-depended tumor cell killing, while cultures of autologous cancer-associated fibroblasts (CAF) enriched for patient-matched non-malignant cells are largely preserved. Ratios represent target-to-TIL concentration. Single-cell sequencing of tumor, involved regional node, and circulating T cells from a HNSCC patient (P120) reveals (d) similar clustering and clonal architecture to HyPR-HN samples, and (e) the conserved presence of TProlif_Tox signature expression in both tumor and node, without expression in blood. f Several TProlif_Tox clonotypes demonstrate identical overlap across primary tumor and involved node but are undetectable in blood. Pre-ex Pre-exhausted T cells, Reg Regulatory T cells, Prolif Proliferative T cells, ExCD8 Exhausted CD8 T cells, ExCD4 Exhausted CD4 T cells, IFN Type I interferon responsive T cells, HSP Heat-shock protein-enriched T cells, SCM stem-cell memory T cells, EM effector memory T cells, CM central memory T cells. Graphic created in BioRender. Zenga, J. (2025) https://BioRender.com/qj8bqqo.
