Immune Response and the Tumor Microenvironment: How They Communicate to Regulate Gastric Cancer

Abstract

Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world's population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.

Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer

“…Recent findings have shown that even in the absence of H. pylori infection, chronic inflammation can promote gastric oncogenesis [1]. Multiple genetic and epigenetic alterations in GC patients have been strongly associated with host immune responses [12]. Appropriate host T cell immunity is critical in response to and clearance of Helicobacter infection.…”

“…Both exogenous stimuli, such as infection with microbes, and endogenous factors result in TSLP production. Previous studies demonstrated that H. pylori infection directly induced TSLP production from human gastric epithelial cells [12,24]. Recent research showed that TSLP could be involved in the progression of breast, lung, pancreatic, and cervical cancers; however, the regulatory mechanisms of TSLP in these cancers are not well defined [25][26][27][28].…”

“…Th2 cells are associated with immune regulation and promote antibody-mediated immune responses, which protect against intestinal helminthic worms. Th17 cells defend against extracellular bacteria and can exacerbate inflammation, while regulatory T cells (Treg) can inhibit inflammation and immune responses [7,11,12]. Infection with Helicobacter pylori (H. pylori) considerably increases the risk of developing GC; however, it alone is not sufficient to induce gastric cancer in humans.…”

The Role of Baseline Inflammatory Response Biomarkers in Predictingthe Prognosis in No Metastatic Gastric Cancer Patients Treated with Preoperative Chemoradiation

“…Moreover, the heterogeneous prognosis among gastric cancer patients necessitated the seek of effective biomarkers for the early detection and outcome prediction. Recently, chronic inflammation was found to plays a critical role in the initiation and progression of numerous cancers, including gastric cancer [15,16]. Interestingly, cancer cells can recruit and activate various leukocytes (especially neutrophils and monocytes) by T cells, specific chemokines and prostaglandins [17][18][19][20].…”

Tumor suppressor miR-449a inhibits the development of gastric cancerviadown-regulation of SGPL1

“…At present, it has been considered that the occurrence of GC is closely related to Helicobacter pylori infection, gene mutation, diet, and other risk factors. [3][4][5] Despite much progress in the treatment of GC, the overall 5 year survival rate of patients with GC is still less than 30%. 6 Heterogeneity and a lack of effective therapeutic targets are the two major obstacles to the precise treatment of GC.…”