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The concept of the tumor microenvironment (TME) dates back to 1863 when Rudolf Virchow established a connection between inflammation and cancer. However, it was not until 1889 that Stephen Paget's seed and soil theory introduced the important role of TME in cancer metastasis, highlighting the intricate relationship between tumors and their surrounding microenvironment.
Tumor infiltration by lymphocytes is seen as a reflection of a tumor-related immune response. [5] There is increasing evidence that biological vesicles (e.g., exosomes) secreted by tumour cells help to foster an immunosuppressive tumour microenvironment. [ 6 ]
Another model has been described in tumor cells in an obesity model called Warburg effect inversion. Whereas in the reverse model, the stroma of the microenvironment produces energy-rich nutrients, in a context of obesity these nutrients already exist in the bloodstream and in the extracellular fluid (ECF).
The composition of monocyte-derived macrophages and tissue-resident macrophages in the tumor microenvironment depends on the tumor type, stage, size, and location, thus it has been proposed that TAM identity and heterogeneity is the outcome of interactions between tumor-derived, tissue-specific, and developmental signals. [2]
The cancer stem cell model, also known as the Hierarchical Model proposes that tumors are hierarchically organized (CSCs lying at the apex [6] (Fig. 3).) Within the cancer population of the tumors there are cancer stem cells (CSC) that are tumorigenic cells and are biologically distinct from other subpopulations [7] They have two defining features: their long-term ability to self-renew and ...
A cancer-associated fibroblast (CAF) (also known as tumour-associated fibroblast; carcinogenic-associated fibroblast; activated fibroblast) is a cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines.
Tumor stroma and extracellular matrix in hypoxia. Tumor hypoxia is the situation where tumor cells have been deprived of oxygen.As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues.
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. [5] TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. [6]