Tumor Microenvironment in Cancer Biology: A Comprehensive Review of Stromal, Immune, and Vascular Components Driving Malignancy

Abstract

The tumor microenvironment (TME), comprising the extracellular matrix (ECM), stromal cells, immune cells, and vascular components, plays a decisive role in cancer growth, metastasis, and treatment response. Although cancer research has traditionally focused on tumor cells, increasing evidence shows that the TME actively influences tumor behavior. This narrative review synthesizes recent findings on the stromal, immune, and vascular elements of the TME, drawing on advanced approaches such as single-cell RNA sequencing and AI-assisted imaging. Cancer-associated fibroblasts (CAFs) promote tumor progression through ECM remodeling and immune suppression, while vascular abnormalities limit drug delivery and contribute to therapeutic resistance. Emerging TME-targeted strategies, including anti-angiogenic agents, immune checkpoint inhibitors, and stromal-directed therapies, show promise but remain challenged by TME heterogeneity and tumor adaptability. The evidence indicates that targeting the TME represents a major shift in cancer therapy and offers important opportunities to develop more effective and personalized treatment strategies.