A) Kaplan-Meier survival curves of TripleMut mice injected with 50 mg/kg tamoxifen, and then treated with daily intraperitoneal ornithine, vehicle, isotype control, or anti-PDL1. Significance is compared to vehicle isotype control (n=5–7). B and C) Flow cytometry analysis from TripleMut mice treated with ornithine, IgG, or anti-PD-L1 therapy for 7 days. (n=3). D) Human tumor samples were binned into OTC high, or OTC low and overall survival was assessed based on cytotoxic T cell scores. (n=62). E) Kaplan-Meier survival curves of PD-L1 treated cancer cohort stratified into high and low ammonia gene signature (n=426). F) Representative OTC staining and G) Kaplan-Meier patient survival based on OTC low and high staining following immunotherapy. Survival significance is calculated using log-rank test. H) Schematic summary of the role of ammonia accumulation in CRC progression. *p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 unless otherwise indicated. Data is presented as mean ± SEM. All experiments were performed in triplicates at least three times.