Recent data suggest that both anti-PD-1 and anti-CTLA-4-based antibody therapies may inadvertently lead to the activation and proliferation of Tregs30–32, and this has been associated with non-responsiveness to anti-PD-1 in NSCLC, gastric cancer and melanoma patients29,32, and hyperprogression upon anti-PD-1 in gastric cancer patients33. This evidence concerns the gene CTLA4 and gastric cancer.