为了探讨免疫稳态受损对皮肤鳞状细胞癌（cSCC）发生和发展的巨大影响，并研究细胞成分的特征及其变化​​，这对于了解 HPV 诱导的 cSCC 的病理过程至关重要。对一名非常罕见的 HPV 诱发的 cSCC 患者进行了诊断和随访，该患者进展速度非常快，并很快转移至死亡。我们对这名 HPV 感染后四种不同皮肤状态的患者皮肤组织中的 11 379 个细胞进行了单细胞 RNA 测序 (scRNA-seq)。使用免疫荧光实验进行验证。 scRNA-seq 发现 CD52 HLA-DOA-巨噬细胞仅存在于癌旁皮肤鳞状细胞癌 (pc-cSCC) 和 cSCC 组织中。此外，CD8耗竭性T细胞、CD4调节性T细胞等免疫细胞以及MMP1、MMP11成纤维细胞等基质细胞也逐渐增多。同时，COMP ASPN成纤维细胞逐渐减少。细胞相互作用分析揭示单核细胞/巨噬细胞、成纤维细胞和肿瘤特异性角质形成细胞之间的相互作用增强。首次在 HPV 诱导的 cSCC 中进行 scRNA-seq，以探讨感染与肿瘤之间的相关性。这是首次研究HPV诱导的cSCC不同感染阶段的肿瘤发展。本研究对肿瘤本身和肿瘤微环境进行了分析和探索。并且它在不同患者的临床样本中得到了验证。我们的研究结果揭示了从正常皮肤到 cSCC 组织的动态免疫稳态，这种改变可能会驱动 HPV 诱导的 cSCC。© 2024 John Wiley

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.© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.