tumormicroenvironment

The tumor microenvironment (TME) refers to the non-cancerous cells, signals, and structures surrounding a tumor that interact with cancer cells. It includes stromal cells, immune cells, endothelial cells, extracellular matrix, and soluble factors such as cytokines and chemokines. The TME is dynamic, influencing tumor initiation, progression, and response to treatment.

Cellular components include cancer-associated fibroblasts (CAFs) that remodel ECM and secrete growth factors; immune cells such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells, cytotoxic T cells, and natural killer cells; endothelial cells that contribute to angiogenesis. The cross-talk among these cells and cancer cells fosters proliferation, survival, invasion, and immune evasion.

Biochemical features include hypoxia-driven metabolic reprogramming, lactic acidosis, and nutrient depletion. Hypoxia-inducible factors upregulate pro-angiogenic and pro-survival pathways. The extracellular matrix is remodeled by matrix metalloproteinases and other enzymes, enabling invasion and metastasis.

The TME also influences metastatic spread by preparing distant niches; it modulates response to therapy, as immune suppression and stromal barriers can limit drug delivery and efficacy.

Therapeutic implications: strategies target the TME such as anti-angiogenic agents, immune checkpoint inhibitors, CAF targeting, ECM-modulating therapies, and combinations to overcome resistance. TME biomarkers are used to predict prognosis and treatment response.