Fig. 4: Tumor cell intrinsic Uchl5 deficiency remodels extracellular matrix.

A Schematic of in vivo RNA-seq and Principal-component analysis (PCA) of replicate samples from RNA-seq analysis of control and Uchl5 KO MOC1-esc1 tumor cells purified from bulk tumor with or without PD1 treatment at day 15. Circles or triangles represent samples, n = 3 tumors for control groups and Uchl5 KO untreated group, 2 tumors for Uchl5 KO anti-PD1 treated, figure created in BioRender¹¹³. B Heatmap illustrating hierarchical clustering and significantly differentially expressed genes in purified MOC1-esc1 cells from in vivo control and Uchl5-deficient tumors with or without anti-PD1 treatment. C Lollipop plot of gene set enrichment analysis showing the top 8 depleted and top 4 enriched gene sets in MOC1-esc1 cells isolated from Uchl5-deficient tumors relative to control tumors. D Mountain plots showing enrichment score for the Core Matrisome, hallmark EMT and partial-EMT gene sets in Uchl5-deficient cells relative to control cells isolated from in vivo tumors under anti-PD1 treatment. Extracellular matrix genes are called out. Data in B-D represent one experiment. E Schematic of single cell analysis from human HNSCC patients (n = 13 patients, 1711 cells). F Lollipop plot showing the top gene sets positively and negatively correlated with UCHL5 expression in malignant cells from scRNA-seq of human patient head and neck tumors. G Schematic of histology analysis of tumor samples from clinical trials (n = 51 patients). H Representative imaging of Hematoxylin and Eosin (H&E) staining of pretreatment tissue biopsies from patients enrolled in the clinical trials with or without Stromal Desmoplasia. Pie Chart Illustrating Post-Treatment Regression (PTR) Rates among patients with and without Stromal Desmoplasia. pTR-0: <10%; pTR-1: 10% − 50%; pTR-2: > 50%.