Department of Health Science, General Surgery, Magna Graecia University, Medicine School of Germaneto, 88100 Catanzaro, Italy.
Department of Translational Medical Sciences (DISMET) and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2019 Apr 29;20(9):2106. doi: 10.3390/ijms20092106.
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.
每年有近 100 万名新患者被诊断出患有胃癌，它仍然是全球癌症相关死亡的第二大主要原因。尽管胃癌代表了一组异质性疾病，但慢性炎症已被证明在肿瘤发生中起作用。癌症的发展是一个多步骤的过程，其特征是在肿瘤起始和进展过程中发生遗传和表观遗传改变。基质微环境对于维持正常组织内稳态或促进肿瘤发展很重要。大量的免疫细胞（即淋巴细胞、巨噬细胞、肥大细胞、单核细胞、髓源性抑制细胞、Treg 细胞、树突状细胞、中性粒细胞、嗜酸性粒细胞、自然杀伤 (NK) 和自然杀伤 T (NKT) 细胞）是胃癌微环境的组成部分。胃癌中肥大细胞密度增加，并且与血管生成、转移性淋巴结数量以及这些患者的生存有关。肥大细胞通过释放血管生成（VEGF-A、CXCL8、MMP-9）和淋巴管生成因子（VEGF-C 和 VEGF-F）在胃癌中发挥促肿瘤作用。胃肥大细胞表达程序性死亡配体（PD-L1 和 PD-L2），这些配体在癌症中作为免疫检查点是相关的。针对免疫检查点的几种临床前试验可能是胃癌的一种创新治疗策略。阐明不同人类胃癌中肥大细胞亚群的作用将需要进行超出评估肥大细胞密度和微定位的复杂性不断增加的研究。
