肿瘤微环境稳态重塑可阻抑肿瘤进展

Remodeling homeostasis of tumor microenvironment to suppress tumor progression

肿瘤的发生、发展、侵袭和转移等生物学行为与其所处环境——肿瘤微环境(TME)密切相关。TME是肿瘤细胞生存和增殖的内环境,囊括了临近的血管网络、免疫细胞、成纤维细胞、信号分子以及细胞外基质等要素,这些因素共同影响着肿瘤的起始、演进、扩散以及对抗肿瘤治疗反应。在肿瘤发展的复杂过程中,TME的稳态失衡是常见现象,表现为缺氧、慢性炎症和免疫抑制等动态变化,逆转稳态失衡并重构“正常化”TME,即所谓的微环境稳态重塑决定着恶性肿瘤的发展与转归。因此,探究TME稳态重建机制,恢复其稳态平衡和免疫重建是抑制恶性肿瘤进展、克服免疫逃逸和逆转肿瘤耐药的关键。本文综述了TME的研究历程,分析了TME构成异质性与动态变化特征。从TME稳态重塑这一科学问题出发,探讨了靶向TME的研究进展,并对其存在问题及未来聚焦方向进行了深入讨论,以期为肿瘤防治提供新策略。

Biological behaviors such as occurrence,development,invasion and metastasis of tumors are closely related to their surrounding environment 0x0E䥺Symbol~B@0x0F tumor microenvironment(TME).TME is the internal environment for the survival and proliferation of tumor cells,including adjacent vascular networks,immune cells,fibroblasts,signaling molecules,and extracellular matrix,which synergistically affect tumor's initiation,evolution,spread,and response to anti-tumor therapy.In the complex process of tumor development,TME dyshomeostasis is a common phenomenon,manifested by dynamic changes such as hypoxia,chronic inflammation,and immunosuppression.Reversing dyshomeostasis and remodeling“normalized”TME,that is,the so-called homeostasis remodeling of microenvironment,determines the development and outcome of malignant tumors.Therefore,exploring the remodeling mechanism of TME homeostasis and restoring its homeostasis and immune reconstitution are the keys to inhibiting the progression of malignant tumors,overcoming immune evasion,and reversing tumor drug resistance.This paper reviews the research history of TME and analyzes its heterogeneity and dynamic change characteristics.It starts from the scientific challenge of TME homeostasis remodeling,explores the advancements in targeted TME research,and provides an in-depth discourse on existing problems and future focus directions,in order to provide new strategies for the prevention and treatment of tumor.