Anderson Ronald, Mkhize Nomzamo M, Kgokolo Mahlatse M C, Steel Helen C, Rossouw Theresa M, Anderson Lindsay, Rapoport Bernardo L
The Clinical and Translational Research Unit, The Medical Oncology Centre of Rosebank, Saxonwold, Johannesburg 2196, Gauteng, South Africa.
Department of Dermatology, Faculty of Health Sciences, University of Pretoria, Prinshof, Pretoria 0084, Gauteng, South Africa.
Cancers (Basel). 2025 May 19;17(10):1702. doi: 10.3390/cancers17101702.
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）的发病率不断上升，加上转移和复发带来的严重风险，凸显了识别新疗法和经过验证的生物标志物以改善患者管理的重要性，尤其是在已确诊的晚期疾病背景下。在简要概述了广为人知的cSCC流行病学、临床特征和诊断之后，本综述重点关注风险因素，最主要的是过度暴露于紫外线辐射（UVR），这是持续性促肿瘤诱变的原因，以及免疫抑制。综述的下一阶段包括评估在cSCC发病机制中寻找关键驱动突变，包括这些突变和其他突变在免疫反应性新表位形成中的作用。关于肿瘤发生的其他机制，免疫逃逸被优先考虑，特别是免疫抑制的无细胞和浸润性细胞介质的参与。前者中突出的是细胞因子转化生长因子-β1（TGF-β1）、前列腺素类前列腺素E2和新兴的免疫抑制核苷腺苷。在后者的情况下，肿瘤浸润和循环调节性T细胞被认为是关键因素。综述的最后部分重点介绍了已确诊和晚期疾病免疫治疗的最新情况，以及寻找有潜力指导患者管理的新型、可靠的病变和全身生物标志物。
