Helicobacter pylori (H. pylori) infection stands out as one of the most prevalent bacterial infections globally, affecting over half of the world's population [1]. The correlation between H. pylori infection and gastric cancer exhibits substantial variability across different regions worldwide. In developing countries, infection rates and gastric cancer incidence tend to be higher, contrasting with the relatively lower rates observed in developed countries. Typically acquired during childhood, H. pylori infection has the potential to persist throughout an individual's lifetime. The onset of gastric cancer often occurs several decades after the initial infection. Notably, H. pylori infection serves as a significant risk factor for the development of gastric cancer [2]. Other contributing factors encompass smoking, dietary habits (including high-salt and high-fat diets), gastric polyps, chronic gastritis, family history, and additional variables. The pathogenicity of H. pylori lies in its ability to induce damage to the gastric mucosa through chronic inflammation and the production of carcinogenic substances such as bacterial toxins and virulence factors, ultimately fostering the progression of gastric cancer [3], [4].

Chronic gastritis resulting from Helicobacter pylori infection can instigate the infiltration of immune cells such as lymphocytes, plasma cells, and macrophages.Changes in the types and quantities of these immune cells within gastric cancer tissues are closely intertwined with tumor development and prognosis [5]. Helicobacter pylori infection exerts its influence on immune responses through diverse mechanisms. It can impede the activity of immune cells, disrupt antigen presentation and T cell responses, and interfere with the expression of immune-related genes [6], [7], [8]. These regulatory effects may significantly impact the initiation and progression of gastric cancer. Helicobacter pylori infection might induce alterations in the expression of immune genes, encompassing cytokines, immune-related receptors, and signaling pathways. Such genetic changes could play a role in the onset and advancement of gastric cancer. Investigations into immunotherapy strategies targeting Helicobacter pylori infection for the prevention or treatment of gastric cancer are underway. These strategies encompass vaccination, immune modulators, and immune checkpoint inhibitors, all aimed at enhancing the immune microenvironment and bolstering immune responses [9], [10]. Despite the demonstrated therapeutic efficacy of immune checkpoint inhibitors in various cancer types, their clinical application in Helicobacter pylori-associated gastric cancer encounters ongoing challenges.

While studies have extensively explored the role of immune cell infiltration and various immune cell types in Helicobacter pylori-associated gastric cancer, research specifically focusing on distinct subgroups of immune cells (such as different T cell subsets, macrophages, plasma cells, etc.) remains relatively limited. Analyzing diverse subgroups of immune cells holds the potential to yield more nuanced and detailed insights. Despite the demonstrated therapeutic effects of immune checkpoint inhibitors in other cancer types, their clinical application in Helicobacter pylori-associated gastric cancer encounters persistent challenges. Consequently, there is an urgent imperative to identify potential targets for immunotherapy specific to Helicobacter pylori-associated gastric cancer.

In this study, our approach involved two main steps. Firstly, we conducted a comprehensive analysis of differential gene expression using the GSE116312 dataset, encompassing data on both Helicobacter pylori gastritis and gastric cancer. Subsequently, we cross-referenced this dataset with the ImmPort immune gene dataset, resulting in the identification of 60 immune genes. Secondly, leveraging these 60 immune genes, we categorized gastric cancer into two distinct subtypes. Intriguingly, these subtypes demonstrated associations with either immune infiltration or tumor mutations. Finally, we utilized the identified 60 immune genes to construct a gastric cancer risk prognosis model. Notably, within this model, we pinpointed two genes, namely THBS1 (thrombospondin 1) and PDGFD (platelet-derived growth factor D), exhibiting high expression in fibroblasts. In conclusion, our study unveils THBS1 and PDGFD as potentially valuable genes in deciphering the immune microenvironment intricacies of Helicobacter pylori-associated gastric cancer.