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.