The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM—specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens—promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME’s potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.
肿瘤微环境（TME）是由细胞和细胞外基质（ECM）成分组成的复杂集合体，在驱动肿瘤进展、影响治疗反应及调控转移过程中发挥着关键作用。本文聚焦于皮肤鳞状细胞癌（cSCC）的肿瘤间质，系统阐述其核心构成要素及其动态作用机制。我们深入探讨cSCC细胞外基质中纤维连接蛋白、透明质酸、层粘连蛋白、蛋白聚糖和胶原蛋白的显著变化如何促进癌症进展、转移及耐药性产生。同时剖析cSCC肿瘤微环境中的细胞组成，详细阐释癌症相关成纤维细胞（CAFs）、间充质干细胞（MSCs）、内皮细胞、周细胞、脂肪细胞及各类免疫细胞群体之间复杂的相互作用网络，揭示这些异质性组分如何共同调控肿瘤发展、血管生成及免疫应答。最后，我们着重强调肿瘤微环境作为治疗靶点的潜在价值。本综述讨论的新兴策略包括：免疫系统调控（过继细胞移植、检查点阻断）、抑制肿瘤血管生成、干扰CAF活性以及调控ECM组分。这些治疗途径凸显了阐明肿瘤微环境相互作用机制对推进cSCC治疗进展的重要意义。未来通过深入揭示这些复杂相互作用网络，将为开发更有效的cSCC治疗方案开辟新路径。
The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression
肿瘤(癌症)患者之家