Emerging Role of Helicobacter pylori in the Immune Evasion Mechanism of Gastric Cancer: An Insight Into Tumor Microenvironment-Pathogen Interaction

Abstract

Helicobacter pylori (H. pylori) infection is the strongest causative factor of gastric cancer. Growing evidence suggests that the complex crosstalk of H. pylori and the tumor microenvironment (TME) exerts a profound influence on gastric cancer progression. Hence, there is emerging interest to in-depth comprehension of the mechanisms of interplay between H. pylori and the TME. This review discusses the regulatory mechanisms underlying the crosstalk between H. pylori infection and immune and stromal cells, including tumor-associated macrophages (TAMs), neutrophils, dendritic cells, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, B and T cells, cancer associated fibroblasts (CAFs), and mesenchymal stem cells (MSCs), within the TME. Such knowledge will deepen the understanding about the roles of H. pylori in the immune evasion mechanism in gastric cancer and contribute to the development of more effective treatment regimens against H. pylori-induced gastric cancer.

Research Progress of Intestinal Microecology in the Pathogenesis of Colorectal Adenoma and Carcinogenesis

“… 95 H. pylori can secrete a variety of virulence factors, which can act on the mucosa and maintain the continuous infection of H. pylori , resulting in tissue damage and chronic inflammatory reaction. 96 CagA exists in the highly virulent strain of H. pylori , and its expression product CagA protein is an important virulence factor for the pathogenic effect of H. pylori . The pro-inflammatory factors released by CagA protein may promote the proliferation of colorectal epithelial cells, leading to colorectal adenomas in CagA + H. pylori -infected people.…”

The Roles of Innate Lymphoid Cells in the Gastric Mucosal Immunology and Oncogenesis of Gastric Cancer

“…They can directly downregulate the natural cytotoxicity by diminishing the ability of NK cells to produce IFN-γ and IL-2, accompanied by lacking CD3 − CD56 + CD25 + NK cells [ 103 ], while retaining IL-10 production, represented by CD8 − CD16 − CD56 bright NK cells [ 104 ]. Additionally, perforin production by NK cells is downregulated [ 105 ]. Interestingly, H. pylori can even directly promote the growth of gastric cancer through the LPS–TLR4 pathway, and vice versa, the neutralization of TLR4 can suspend this proliferative activity [ 106 ].…”

IL-6 facilitates cross-talk between epithelial cells and tumor- associated macrophages in Helicobacter pylori-linked gastric carcinogenesis

“…Importantly, the IL-6/STAT3 axis is also involved in the polarization of macrophages, which are believed to be mediators in H. pylori -associated gastritis [22] , through release of IL-6 [ 22 , 23 ]. The presence of macrophages, particularly those of the M2 type associated with immune evasion, is a characteristic of stomach carcinomas [24] and has been linked to the likelihood of disease development and mortality [25] , [26] , [27] .…”