Fig. 4: PIGR⁺ epithelial cells are enriched in HPV⁺ PSCC and are induced by IFNγ.

A Heatmap displaying large-scale copy number variations (CNVs) for individual epithelial cells (rows) from NATs and tumors, with red indicating amplifications and blue indicating deletions. B UMAP plot of 9,255 malignant epithelial cells, showing five clusters colored by cell type (left) and HPV status (right). C Bar graph showing the relative proportions of each cluster by HPV status. D Differential gene analysis of cluster 5, with upregulated marker genes highlighted in red. E UMAP plot showing the cluster 5 specifically expressed genes PIGR. F Gene Ontology (GO) analysis of higher expressed marker genes in cluster 5. G Bar graph showing the relative proportion of IHC scores for PIGR in HPV^- (n = 52) and HPV⁺ (n = 33) PSCC tumor sections. H Mean IHC score and representative IHC staining images of PIGR in HPV^- (n = 52) and HPV⁺ (n = 33) PSCC tumor specimens (****P < 0.0001). Scale: 100 μm. I Representative immunofluorescence staining for PIGR, IgA and DAPI⁺ nuclei in HPV^- and HPV⁺ PSCC tumor. Scale: 300 μm. J Quantification of IgA-PIGR colocalization events in HPV⁻ (n = 20) and HPV⁺ (n = 20) PSCC samples (****P < 0.0001). K Representative H&E and IHC staining for malignant epithelial differentiation (CK, CK5/6, VIM and KI67) and squamous cell origin (P40) in PSCC tumor tissues (top) and PSCC patient derived primary cells (bottom). Scale: 200 μm. L Quantitative analysis of PIGR mRNA level with various factors treatment (n = 3 independent experiments, IgAG **P = 0.0036, IgA: *P = 0.0190, IL-1β: **P = 0.0052, TNF-α: **P = 0.0029, IFN-β: **P = 0.0028, IFN-γ: **P = 0.0018). M Quantitative analysis of PIGR protein level with IFNγ treatment. N Bar graph showing the relative proportions of IHC scores for IFNγ in HPV^- (n = 28) and HPV⁺ (n = 28) PSCC tumor sections. O Mean IHC score and representative IHC staining images of IFNγ in HPV^- (n = 28) and HPV⁺ (n = 28) PSCC tumor specimens (****P < 0.0001). Scale: 100 μm. P–R Pearson correlation analysis of IHC scores between PIGR and IFNγ (P), PIGR and IgG (Q), PIGR and IgA (R) in PSCC tumor sections (****P < 0.0001). A two-sided unpaired Student’s t test was used in (H), (J), (L) and (O). Pearson Correlation analysis with two-tailed was used in (P–R). Data are presented as mean ± s.e.m. ns: not significant (P > 0.05). Source data are provided as a Source Data file.