Abstract:
The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in the TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse and influential roles. CAFs are activated fibroblasts found abundantly within the TME of various cancer types. CAFs contribute significantly to tumor progression by promoting angiogenesis, remodeling the extracellular matrix, and modulating immune cell infiltration. In order to influence the microenvironment, CAFs engage in cross-talk with immune cells, cancer cells, and other stromal components through paracrine signaling and direct cell-cell interactions. This cross-talk can result in immunosuppression, tumor cell proliferation, and epithelial-mesenchymal transition, contributing to disease progression. Emerging evidence suggests that CAFs play a crucial role in therapy resistance, including resistance to chemotherapy and radiotherapy. CAFs can modulate the tumor response to treatment by secreting factors that promote drug efflux, enhance DNA repair mechanisms, and suppress apoptosis pathways. This paper aims to understand the multifaceted functions of CAFs within the TME, discusses cross-talk between CAFs with other TME cells, and sheds light on the contibution of CAFs to therapy resistance. Targeting CAFs or disrupting their cross-talk with other cells holds promise for overcoming drug resistance and improving the treatment efficacy of various cancer types.
摘要:
肿瘤微环境(TME)是一个复杂的细胞生态系统,信号分子,和对癌症进展有深远影响的细胞外基质成分。在TME的关键人物中,癌症相关成纤维细胞(CAFs)因其多样化和有影响力的作用而受到越来越多的关注。CAF是在各种癌症类型的TME中大量发现的活化的成纤维细胞。CAFs通过促进血管生成显著促进肿瘤进展,重塑细胞外基质,和调节免疫细胞浸润。为了影响微环境,CAF与免疫细胞进行交叉对话,癌细胞,和其他基质成分通过旁分泌信号和直接的细胞-细胞相互作用。这种串扰会导致免疫抑制,肿瘤细胞增殖,和上皮-间质转化,有助于疾病进展。新的证据表明,CAF在治疗抵抗中起着至关重要的作用,包括对化疗和放疗的抗性。CAFs可以通过分泌促进药物外排的因子来调节肿瘤对治疗的反应,增强DNA修复机制,并抑制凋亡途径。本文旨在了解CAF在TME中的多方面功能,讨论了CAF与其他TME细胞之间的串扰,并阐明了CAF对治疗抗性的影响。靶向CAF或破坏它们与其他细胞的串扰有望克服耐药性并提高各种癌症类型的治疗功效。