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Helicobacter pylori is one of the main predisposing factors for gastric cancer, causing chronic inflammation and proper glands atrophy in the gastric mucosa. Although H. pylori‐induced inflammation is a key inducer of precancerous lesions in the gastric mucosa, it remains unclear which precise immune cell subsets are responsible for the progression of H. pylori‐induced gastritis. Here, we observed an abundance of CD4+IL‐17A+FOXP3+ T cells exhibiting a Th17‐like phenotype within the microenvironment of H. pylori‐induced gastritis. Mechanistically, H. pylori upregulated the expression of IL‐6 in Dendritic cells and macrophages, by activating NF‐κB signaling through the virulence factor CagA and thus, induced IL‐17A expression in FOXP3+ T cells. Moreover, CD4+IL‐17A+FOXP3+ T cells were positively associated with advanced precancerous lesions. Therefore, these findings offer essential insights into how FOXP3+ T cells sense inflammatory signals from the environment, such as IL‐6, during H. pylori infections, thereby guiding the effector immune response and aggravating the gastritis. [ABSTRACT FROM AUTHOR]

Existing immune checkpoint inhibitors focus on activating T cells and show limited effectiveness in gastric cancer (GC). SIGLEC10 is identified as a novel tumor-associated macrophage-related immune checkpoint in other cancer types. However, its immunosuppressive role and clinical significance in GC remain unclear. In this study, we find a dominant expression of SIGLEC10 on CD68+ macrophages in GC. SIGLEC10 can suppress the proliferation and function of tumor-infiltrating CD8+ T cells in vitro via the Akt/P38/Erk signaling pathway. Furthermore, in ex vivo and in vivo models, SIGLEC10 blockade promotes CD8+ T cell effector function. Finally, SIGLEC10+ macrophages are positively correlated with the adverse prognosis of GC. Our study highlights that SIGLEC10 directly suppresses T cell function and serves as a promising target for immunotherapy and suggests SIGLEC10+ macrophages as a novel potential predictor of the clinical prognosis of GC. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is one of the main predisposing factors for gastric cancer, causing chronic inflammation and proper glands atrophy in the gastric mucosa. Although H. pylori-induced inflammation is a key inducer of precancerous lesions in the gastric mucosa, it remains unclear which precise immune cell subsets are responsible for the progression of H. pylori-induced gastritis. Here, we observed an abundance of CD4 + IL-17A + FOXP3 + T cells exhibiting a Th17-like phenotype within the microenvironment of H. pylori-induced gastritis. Mechanistically, H. pylori upregulated the expression of IL-6 in Dendritic cells and macrophages, by activating NF-κB signaling through the virulence factor CagA and thus, induced IL-17A expression in FOXP3 + T cells. Moreover, CD4 + IL-17A + FOXP3 + T cells were positively associated with advanced precancerous lesions. Therefore, these findings offer essential insights into how FOXP3 + T cells sense inflammatory signals from the environment, such as IL-6, during H. pylori infections, thereby guiding the effector immune response and aggravating the gastritis., (© 2024 Wiley-VCH GmbH.)