The impact of ICOS⁺ regulatory T cells and Helicobacter pylori infection on the prognosis of patients with gastric and colorectal cancer: potential prognostic benefit of pre-operative eradication therapy

It remains unclear whether Helicobacter pylori (H. pylori), a major cause of gastric cancer (GC), is involved in other intestinal cancers. In our previous study, ICOS⁺ Foxp3⁺ CD4⁺ T cells (ICOS⁺ Tregs) in GC tumors were identified as effector Tregs and associated with H. pylori. In the present study, the impact of ICOS⁺ Tregs on not only GC, but also colorectal cancer (CRC) and their prognosis was investigated in association with H. pylori. Tissue-infiltrating lymphocytes (TILs) purified from fresh tumor and sera were obtained from GC and CRC patients prospectively. % ICOS⁺ Tregs were analyzed by flow cytometry and their production of anti-H. pylori antibody (Hp-Ab) in sera was detected by ELISA. % ICOS⁺ Tregs were higher in GC and CRC patients with Hp-Ab than in those without Hp-Ab, including eradicated patients. ICOS⁺ Tregs purified had higher potential to produce IL-10 than ICOS^- Tregs. For prognostic analysis, immunohistochemical analysis and ELISA were performed using archival fixed specimens and frozen sera, respectively, obtained from GC and CRC patients. Overall survival was longer in patients with low % ICOS⁺ Tregs than in those with high % ICOS⁺ Tregs, and patients with Hp-Ab showed shorter recurrence-free survival than those without Hp-Ab. These results suggested that ICOS⁺ Tregs in GC and CRC patients were closely associated with H. pylori in gastric epithelium and their prognosis, and that pre-operative H. pylori eradication has potential as a novel immunotherapy for GC and CRC patients.