Single cell transcriptomics reveals dysregulated immnue homeostasis in different stages in <scp>HPV</scp> ‐induced cutaneous squamous cell carcinoma

In order to explore the huge impact of impaired immnue homeostasis on the occurrence and development of cutaneous squamous cell carcinoma (cSCC), and investigate characterization of the cellular components and their changes which is crucial to understanding the pathologic process of HPV-induced cSCC, we diagnosed and followed up on a very rare HPV-induced cSCC patient who progressed at a very fast rate and transferred to death quickly. We performed single-cell RNA sequencing (scRNA-seq) of 11 379 cells from the skin tissues of this patient with four different skin statuses after HPV infection. Immunofluorescence experiments were used for validation. scRNA-seq identified that CD52⁺ HLA-DOA^- macrophages only existed in paracancerous cutaneous squamous cell carcinoma (pc-cSCC) and cSCC tissue. Besides, immune cells including CD8⁺ exhausted T cells and CD4⁺ regulatory T cells as well as matrix cells like MMP1⁺, and MMP11⁺ fibroblasts were gradually increased. Meanwhile, COMP⁺ ASPN⁺ fibroblasts gradually decreased. Cell interaction analysis revealed enhancement in interactions between monocytes/macrophages, fibroblasts and tumour-specific keratinocytes. scRNA-seq was performed in HPV-induced cSCC for the first time, to explore the correlation between infection and tumour. It is the first time to study the development of tumours from different stages of infection in HPV-induced cSCC. In this study, the tumour itself and the tumour microenvironment were both analysed and explored. And it was validated in clinical samples from different patients. Our findings reveal the dynamic immnue homeostasis from normal skin to cSCC tissue, this alteration might drive HPV-induced cSCC.