Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China.
Key laboratory of Microecology-immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang Province, 154007, China.
J Hematol Oncol. 2024 Sep 2;17(1):80. doi: 10.1186/s13045-024-01600-2.
Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into the intrinsic oncogenic mechanisms of the tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) and metabolic reprogramming regulates tumor progression through numerous biological activities, including tumor immunosuppression, chronic inflammation, and ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted and mediators released via CAFs and multiple immune cells that collectively support chronic inflammation, thereby inducing pre-metastatic ecological niche formation, and ultimately driving a vicious cycle of tumor proliferation and metastasis. This review comprehensively explores the process of CAFs and metabolic regulation of the dynamic evolution of tumor-adapted TME, with particular focus on the mechanisms by which CAFs promote the formation of an immunosuppressive microenvironment and support metastasis. Existing findings confirm that multiple components of the TME act cooperatively to accelerate the progression of tumor events. The potential applications and challenges of targeted therapies based on CAFs in the clinical setting are further discussed in the context of advancing research related to CAFs.
代谢重编程为肿瘤提供了能量来源和生物燃料，以支持其在恶性微环境中的存活。对肿瘤微环境（TME）内在致癌机制的广泛研究已经确立，癌相关成纤维细胞（CAFs）和代谢重编程通过多种生物学活性调节肿瘤进展，包括肿瘤免疫抑制、慢性炎症和生态位重塑。具体而言，通过 CAFs 和多种免疫细胞促进免疫抑制性 TME 的形成和介质释放，这些细胞共同支持慢性炎症，从而诱导前转移生态位形成，并最终驱动肿瘤增殖和转移的恶性循环。本综述全面探讨了 CAFs 和代谢对肿瘤适应的 TME 动态演变的调节作用，特别关注 CAFs 促进免疫抑制微环境形成和支持转移的机制。现有研究结果证实，TME 的多个成分协同作用，加速了肿瘤事件的进展。还讨论了基于 CAFs 的靶向治疗在临床环境中的潜在应用和挑战，这是在与 CAFs 相关的研究进展的背景下进行的。
