Activation of CD3(+) T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma

摘要

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3(+) T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3(+) T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3(+) T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8(+)/CD4(+) T cells, reduced infiltration of regulatory FOXP3(+) T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3(+) T cells in those with advanced GC.