Buruiană Alexandra, Gheban Bogdan-Alexandru, Gheban-Roșca Ioana-Andreea, Georgiu Carmen, Crișan Doința, Crișan Maria
Department of Pathology, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Department of Histology, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Cancers (Basel). 2024 Apr 29;16(9):1727. doi: 10.3390/cancers16091727.
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）是细胞和细胞外基质（ECM）成分的复杂组合，在推动肿瘤进展、塑造治疗反应和影响转移方面发挥着关键作用。这篇叙述性综述聚焦于皮肤鳞状细胞癌（cSCC）的肿瘤基质，突出其关键成分及其动态作用。我们研究了cSCC细胞外基质内的显著变化——具体而言，纤连蛋白、透明质酸、层粘连蛋白、蛋白聚糖和胶原蛋白的改变——如何促进癌症进展、转移和耐药性。我们还探讨了cSCC肿瘤微环境的细胞组成，详细阐述了癌症相关成纤维细胞（CAF）、间充质干细胞（MSC）、内皮细胞、周细胞、脂肪细胞和各种免疫细胞群体之间复杂的相互作用。这些不同的参与者调节肿瘤发展、血管生成和免疫反应。最后，我们强调肿瘤微环境作为治疗靶点的潜力。本综述中讨论的新兴策略包括利用免疫系统（过继性细胞转移、检查点阻断）、阻碍肿瘤血管生成、破坏CAF活性和操纵细胞外基质成分。这些方法强调了解码肿瘤微环境相互作用在推进cSCC治疗中所起的重要作用。进一步阐明这些复杂关系的研究将为开发更有效的cSCC治疗方法开辟新途径。
