Tumors have traditionally been regarded as a collection of homogeneous malignant cells. However, modern cancer biology reveals that tumors are complex abnormal organs, whose occurrence, development, metastasis, and therapeutic resistance are profoundly influenced by their surrounding dynamic ecosystem—namely, the tumor microenvironment (TME). The TME consists of various non-tumor cellular components (including immune cells, cancer associated fibroblasts, endothelial cells, etc.), extracellular matrix (ECM), numerous soluble factors (such as cytokines and chemokines), and physicochemical characteristics (such as hypoxia and acidity). Continuous and bidirectional interactions occur among these components as well as between them and tumor cells, collectively shaping a microenvironment that supports tumor growth, promotes immune evasion, enhances invasion and metastasis, and mediates therapeutic resistance. This article aims to systematically describe the core components and functions of the TME, analyze the dynamic evolution of the TME at different stages of tumor progression, and focus on the mechanisms, current status, and challenges of novel TME-targeted therapies (such as immune checkpoint inhibitors, anti-angiogenic therapies, and stroma-targeted therapies). Finally, the article envisions the application prospects of single-cell multi-omics technologies, spatial transcriptomics, and artificial intelligence in elucidating TME heterogeneity and developing next-generation combination therapies. A profound understanding of TME complexity is crucial for advancing cancer treatment from a tumor cell-centered approach to a microenvironment-targeted paradigm.
Gang Liu (Mon,) studied this question.