Brogna Marianna Rita, Varone Valeria, DelSesto Michele, Ferrara Gerardo
Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
Front Mol Biosci. 2025 Mar 31;12:1568865. doi: 10.3389/fmolb.2025.1568865. eCollection 2025.
The tumor microenvironment (TME) is a crucial element of cancerous tissue and has emerged as a promising target for therapeutic strategies. The complex variety of stromal cells within the TME plays a vital role in determining the tumor's aggressiveness and its resistance to treatment. Tumor progression is not solely driven by cancer cells harboring genetic mutations but is also significantly influenced by non-cancerous host cells within the TME, which strongly impact tumor growth, metastasis, and the response to therapies. Cancer-associated fibroblasts (CAFs) are a diverse group of stromal cells within the TME. They play dual roles, both promoting and inhibiting tumor growth, making them intriguing targets for enhancing cancer therapies. Their significant contribution to creating a tumor-supportive environment has diminished the effectiveness of various cancer treatments, including radiation, chemotherapy, immunotherapy, and hormone therapy. Research has increasingly focused on understanding how CAFs contribute to therapy resistance in triple-negative breast cancer (TNBC) to improve treatment outcomes. However, the ways in which CAF patterns affect the TME and the response to immunotherapy in TNBC are not yet well understood and the interactions between CAFs, tumor cells, and immune cells in TNBC remain largely unexplored. In this review, we thoroughly exam ine the relationship between TNBC progression and CAF patterns. We discuss the current understanding of CAF heterogeneity, their role in tumor progression, and their impact on the tumor's response to therapeutic agents in TNBC. Additionally, we explore the potential and possible strategies for therapies targeting CAFs.
肿瘤微环境(TME)是癌组织的关键要素,已成为治疗策略的一个有前景的靶点。TME内复杂多样的基质细胞在决定肿瘤的侵袭性及其对治疗的抗性方面起着至关重要的作用。肿瘤进展不仅由携带基因突变的癌细胞驱动,还受到TME内非癌宿主细胞的显著影响,这些细胞强烈影响肿瘤的生长、转移及对治疗的反应。癌症相关成纤维细胞(CAFs)是TME内一组多样的基质细胞。它们发挥着促进和抑制肿瘤生长的双重作用,使其成为增强癌症治疗的有趣靶点。它们对营造肿瘤支持性环境的重大贡献削弱了包括放疗、化疗、免疫疗法和激素疗法在内的各种癌症治疗的效果。研究越来越关注了解CAFs如何导致三阴性乳腺癌(TNBC)的治疗抗性以改善治疗结果。然而,CAF模式影响TME及TNBC对免疫疗法反应的方式尚未得到充分理解,TNBC中CAFs、肿瘤细胞和免疫细胞之间的相互作用在很大程度上仍未被探索。在本综述中,我们全面研究了TNBC进展与CAF模式之间的关系。我们讨论了目前对CAF异质性的理解、它们在肿瘤进展中的作用以及它们对TNBC中肿瘤对治疗药物反应的影响。此外,我们探索了针对CAFs的治疗的潜力和可能策略。