The increasing incidence of cutaneous squamous cell carcinoma (cSCC), together with the ominous risks of metastasis and recurrence, underscores the importance of identifying novel therapies and validated biomarkers to augment patient management, particularly in the context of well-established and advanced disease. Following a brief overview of the well-recognized epidemiology, clinical features, and diagnosis of cSCC, the current review is focused on risk factors, most prominently excessive exposure to ultraviolet radiation (UVR) as a cause of persistent, pro-tumorigenic mutagenesis, and immune suppression. The next phase of the review encompasses an evaluation of the search for key driver mutations in the pathogenesis of cSCC, including the role of these and other mutations in the formation of immunologically reactive neoepitopes. With respect to additional mechanisms of tumorigenesis, immune evasion is prioritized, specifically the involvement of cell-free and infiltrating cellular mediators of immune suppression. Prominent amongst the former are the cytokine, transforming growth factor-β1 (TGF-β1), the prostanoid, prostaglandin E2, and the emerging immune suppressive nucleoside adenosine. In the case of the latter, tumor-infiltrating and circulating regulatory T cells have been implicated as being key players. The final sections of the review are focused on an update of the immunotherapy of established and advanced disease, as well as on the search for novel, reliable lesional and systemic biomarkers with the potential to guide patient management.
皮肤鳞状细胞癌（cSCC）发病率持续上升，且存在转移与复发的高风险，这凸显了开发新型疗法及验证有效生物标志物以改善患者管理的重要性，尤其是在已确诊及晚期疾病背景下。本文在简要概述cSCC公认的流行病学特征、临床表现及诊断方法后，重点聚焦于其风险因素，其中过度暴露于紫外线辐射（UVR）导致的持续性促肿瘤突变及免疫抑制尤为关键。随后，本文系统评估了cSCC发病机制中关键驱动突变的研究进展，包括这些突变与其他突变在免疫反应性新表位形成中的作用。在肿瘤发生的其他机制方面，重点探讨了免疫逃逸现象，特别是无细胞介质与浸润细胞介导的免疫抑制机制。前者主要包括细胞因子转化生长因子-β1（TGF-β1）、前列腺素类物质前列腺素E2以及新兴的免疫抑制性核苷腺苷；后者则涉及肿瘤浸润性与循环性调节性T细胞的关键作用。本文最后部分重点更新了已确诊及晚期疾病的免疫治疗进展，并探讨了具有临床指导潜力的新型可靠局部与全身生物标志物的研究现状。
肿瘤(癌症)患者之家