Forty-five patients with MSI-H/dMMR GI tumors, including gastric cancer, colorectal cancer, cholangiocarcinoma, small intestine cancer, pancreatic cancer, and duodenal cancer, receiving PD-1 blockade were analyzed....Patients with low tumor mutational burdens (TMBs) had lower objective response rates (ORRs) (0 vs 48.8%) and a significantly shorter progression-free survival (PFS) (2.3 vs 15.6 months; hazard ratio (HR): 6.20, P = 0.002) than those with high TMBs....Low TMBs and PTEN mutations...negative predictors of PD-1 blockade responses in patients with MSI-H/dMMR GI tumors.