tmes

TMEs, or tumor microenvironments, describe the cellular and acellular context in which tumors develop. They include cancer cells and surrounding non-malignant cells such as cancer-associated fibroblasts, immune cells (tumor-associated macrophages, T cells, neutrophils, myeloid-derived suppressor cells), endothelial cells and pericytes, adipocytes, and the extracellular matrix, as well as soluble factors, pH, and oxygen tension.

The interactions are bidirectional and dynamic. TMEs influence cancer cell proliferation, survival, invasion, angiogenesis, and metastasis, and they facilitate immune evasion and therapeutic resistance. The microenvironment is spatially heterogeneous and evolves during disease progression and in response to therapy.

Common mechanisms involve extracellular matrix remodeling by fibroblasts, cytokine signaling such as TGF-β and IL-6, hypoxia-induced factors, and metabolic coupling between cancer and stromal cells. These interactions can create barriers to drug delivery, promote invasive behavior, and support tumor growth through altered nutrition and signaling networks.

Clinical relevance is substantial, as TMEs affect prognosis and treatment response. Therapeutic strategies include anti-angiogenic agents, immune checkpoint inhibitors, and approaches targeting cancer-associated fibroblasts or ECM remodeling. However, redundancy in signaling and potential damage to normal tissues can limit effectiveness, often requiring combination therapies and careful patient selection.

Research methods to study TMEs encompass histology, flow cytometry, single-cell and spatial transcriptomics, and advanced imaging. Experimental models range from in vitro co-culture systems to mouse xenografts and genetically engineered models, enabling dissection of cell–cell interactions and therapeutic testing.

Differences among cancer types are notable; for example, pancreatic ductal adenocarcinoma commonly features a dense desmoplastic stroma, while other tumors may exhibit highly immunosuppressive TMEs or distinctive resident immune populations.