Abstract
Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumour initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumour development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, Treg cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells) are components of gastric cancer microenvironment. Mast cell density is increased in gastric cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. Mast cells exert a protumorigenic role in gastric cancer through the release of angiogenic (VEGF-A, CXCL8, MMP-9) and lymphangiogenic factors (VEGF-C and VEGF-F). Gastric mast cells express the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in gastric cancer. Elucidation of the role of subsets of mast cells in different human gastric cancers will demand studies of increasing complexity beyond those assessing merely mast cell density and microlocalization.
Highlights
Gastric cancer is the fourth-most-common cancer globally and the second-leading cause of cancer deaths [1,2,3]
vascular endothelial growth factors (VEGFs)-A is a potent agonist of vascular endothelial growth factor receptor 2 (VEGFR2) on blood endothelial cells (BECs) [142]
Mast cell density in tumour microenvironment was associated with poor prognosis [129,168,170,198,199,218], tumour angiogenesis [169,198,199,204,219] and the formation of lymph node [168,219] and bone metastases [209]
Summary
Gastric cancer is the fourth-most-common cancer globally and the second-leading cause of cancer deaths [1,2,3]. Mast cell progenitors enter the circulation and complete their maturation in tissues These cells are involved in several physiological and inflammatory processes, including organ development [41], skin barrier homeostasis [42], angiogenesis [43], lymphangiogenesis [44], wound healing [45], heart function [46,47], coagulation [48] and tumorigenesis [35,49,50,51,52,53,54,55]. Mast cell mediators have been canonically associated with a detrimental role in allergic diseases [38,39,57,66] Given their presence in most tissues and the plethora of proinflammatory and immunoregulatory mediators they produce and their capacity to interact closely with several immune and non-immune cells, mast cells are involved in several pathophysiological processes [67]
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