The study “The crosstalk between H. pylori virulence factors and the PD1:PD-L1 immune checkpoint inhibitors in progression to gastric cancer”
conducted by Assoc. Prof. Dr. Ayça Sayı Yazgan and her students from ITU Molecular Biology and Genetics Department (MBG) was published in the journal Immunology Letters.
Chronic infection caused by Helicobacter pylori (H. pylori) has been associated with the progression to gastric cancer. Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death –ligand 1, PD-L1) are involved in escape of cancer from immune surveillance. How H. pylori virulence factors are related with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes have remained elusive. Thus, in this study, effects H. pylori virulence factors on the expression levels of immune-related genes in the development of gastric immunopathology were scrutinized. By performing quantitative real-time PCR (qRT-PCR), the expression of PD-1 and PD-L1 inhibitors, Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes were analyzed for gastric tissues of both normal controls and patients with gastritis, gastric ulcer, and gastric cancer. Moreover, how degree of inflammation and H. pylori density were correlated with genotypes of H. pylori virulence factors’ (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A(babA), duodenal ulcer promoting gene A(dupA); the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) were examined. Afterwards, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Finally, by utilizing expression data, a decision tree model was constructed in order to determine the clinical results of the patients. At the end, it was deduced from the results that levels of immune checkpoint inhibitors PD-1:PD-L1 elevated during the progression of pre-cancerous lesions towards gastric cancer. In this study, by means of computer-based models, the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies is demonstrated.