Tumormilieu

Tumor microenvironment (TME) denotes the cellular and biophysical milieu surrounding a tumor. It encompasses cancer cells and a diverse set of non-m malignant cells, such as cancer-associated fibroblasts, mesenchymal cells, immune cells (T cells, macrophages, dendritic cells, natural killer cells, myeloid-derived suppressor cells), endothelial cells and pericytes, as well as the extracellular matrix, blood vessels, cytokines, chemokines, and growth factors. The TME is characterized by hypoxia, altered pH, and metabolic gradients that influence cell behavior and matrix remodeling.

Interactions between tumor cells and TME components are bidirectional. Tumor cells secrete signals that recruit and reprogram stromal and immune cells; in turn, stromal and immune cells can promote tumor growth, angiogenesis, invasion, and immune evasion. ECM remodeling and angiogenesis support nutrient supply and metastatic spread, while immune cells can either attack tumor cells or, in a pro-tumor environment, support progression through immunosuppressive phenotypes.

Clinical relevance: the TME affects cancer progression and therapy response. Anti-angiogenic therapies, immune checkpoint inhibitors, and strategies aimed at reprogramming cancer-associated fibroblasts or myeloid cells illustrate TME-targeted approaches. Metabolic and mechanical features of the TME also shape drug delivery and efficacy.

Challenges include heterogeneity across tumor types and even within a tumor, dynamic changes during treatment, and context-dependent roles of various TME components, which complicate biomarker development and predictive modeling.