MAST CELL-RELATED DISEASE
Factually, the relation between malignant cells and the TME may result in the progression of tumor growth . The first inflammatory mast cell interacts with entering pathogens are the most important guard of the immune system . It sticks to the phagocyte and executes the innate immunity i.e. Gram-positive and Gram-negative bacteria. The mast cell then initiates its response through the interaction of B cells and T cells, migration, maturation, and the role of dendritic cells . At the site of action, the pro-inflammatory mediators initiate the innate immune response during infection . The mast cells are also engaged in boosting angiogenesis. The pro-angiogenic factors such as VEFG, BFGF, TGF-BETA, TNF-ALPHA and Interleukin-8 are secreted by mast cells. Furthermore, Protease and heparin are discharged by the mast cell which then releases pro-angiogenic factors that bind to heparin. The mast cell release histamine which induces microvascular permeability which in turn induces angiogenesis . The existence of mast cells in the TME is not a fresh finding as Paul Ehrlich previously described them in his doctoral thesis. In certain scenarios depending on the manner of the tumour, mast cells may have an immunosuppressive function by releasing histamine, interleukin-10 and TNF-α. Moreover, mast cells can suppress T cells and NK cells by freeing adenosine into the microenvironment. The penetration of mast cells into the tumour stroma as well as the development and activation of Tregs are stimulated leading to tumour progression . Previous human cell line studies were conducted to aim at the role of mast cells in shaping tumour growth. In patients having non-small lung cancer, mast cells were gathered in the TME both MCTCand MCT are rich in tumours . Similar studies were conducted with patients having colorectal cancer, Breast cancer and other numerous cancer in which researcher’s observed that high rate of tryptase+ mast cell in the tumour, the PA-2 receptor activated by Tryptase which promotes the progression of cancer . In addition, Histamine promotes cell proliferation by acting on the surface of a tumour expressing H1receptor. In solid tumours like thyroid tumours, high engagement of histamine H1R and H2R results in tumour cell proliferation . This can be controlled by preventing the release of linkage or any substances with respective receptors, for instance, the prevention of histamine linkage to the receptors . In other findings, researchers analyzed the distribution of mast cells around the vessel and gland of gastric carcinoma using computer analysis and it was established that in gastric carcinoma grade II, there is a link between chymase+ mast cells and were located at a shorter distance from the vessel. Meanwhile, targets for new therapeutic approaches are very desirable as mast cells are involved in several malignant cancer. Concerning the mechanism of mast cell activation, the free light chains have been examined in numerous models. In murine B16F10 melanoma model inhibition of free light chains-mediated mast cell activation reduces tumour growth . The activity of mast cells can be suppressed by using a mast stabilizing agent or indirectly targeting the mediators of the mast cells. For example, an anti-TNF monoclonal antibody targets the TNF as well as anti-histamine medication to inhibit the action of histamine.