Exploring The Tumour Microenvironment.
What constitute the tumour microenvironment? Interactions between malignant and non-transformed cells create the tumour microenvironment (TME). The non-malignant cells of the TME have a dynamic and often tumour-promoting function at all stages of carcinogenesis. Intercellular communication is driven by a complex and dynamic network of cytokines, chemokines, growth factors, and inflammatory and matrix remodelling enzymes against a background of major perturbations to the physical and chemical properties of the tissue. The evolution, structure and activities of the cells in the TME have many parallels with the processes of wound healing and inflammation, but cells such as macrophages are also found in cancers that have no known association with chronic inflammatory conditions. One reason for this is that inflammatory and wound-healing processes are activated downstream of oncogenic mutations in the malignant cells. Apart from malignant cells, the TME contains cells of the immune system, the tumour vasculature and lymphatics, as well as fibroblasts, pericytes and sometimes adipocytes. These cells are frequently distinguished by cell-type-specific markers, which are often cell surface molecules. The importance of the TME in designing new cancer treatment regimes is now apparent. Targeting several different aspects of the TME during cancer treatment might allow us to reach a ‘tipping point’ where its tumour-promoting and suppressive immune system is disabled or reprogrammed, its chaotic blood supply is normalised or destroyed, and as malignant cells are destroyed, new antigens are uncovered that are recognised by the reawakened immune system. The common features of many TMEs suggest that targeting the non-malignant cells, or mediators of their communication, have applications across different tumour types and could also complement other treatment options. Credit: Frances R. Balkwill, Melania Capasso, Thorsten Hagermann for Journal of Cell Science, 2012.
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