Heterogeneity of T cells regulates tumor immunity mediated by Helicobacter pylori infection in gastric cancer

The impact of Helicobacter pylori (H. pylori) status on gastric cancer survival remains unclear. In this study, we conducted a prognostic analysis of 488 gastric cancer patients and performed single-cell RNA sequencing (scRNA-seq) on 18,717 T cells from six tumor samples with varying H. pylori statuses. Our findings revealed that gastric cancer patients with H. pylori infection had significantly longer survival times compared to those with negative H. pylori status. After unsupervised re-clustering of T cells based on scRNA-seq data, we identified ten CD4⁺ and twelve CD8⁺ clusters. Among them, four CD8⁺ T cell clusters exhibited distinct distributions based on H. pylori infection status. One cluster, marked by CXCL13, showed high levels of IFNG and GZMB in H. pylori-infected patients, while another cluster, which expressed immune suppression related genes like AREG and PTGER2, was predominantly comprised of cells from non-infected patients. High PTGER2 expression was significantly associated with worse prognosis in patients with high CD8 expression. These insights advance our understanding of H. pylori's influence on T cell responses in gastric cancer, aiding in treatment and prognostic strategies.