GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299214/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299214GEOGSEfalseOrphan drug nitisinone combined with sorafenib synergistically boosts anti-PD-1 efficacy in MSS Colorectal Cancer [RNA-Seq]We reveal nitisinone, an FDA-approved tyrosine catabolism inhibitor that targets the HPD enzyme, and sorafenib exert synergistic growth inhibition effects in MSS CRC cells, organoids and mouse xenografts. Using co-cultures of PBMCs with autologous tumor organoids, orthotopic transplant models, multiplex immunostaining and scRNA-seq, we verify that the combination of nitisinone and sorafenib synergistically enhances anti-PD-1 efficacy in a manner that is dependent on the mtDNA-cGAS-STING axis and recruits and activates NK cells. Collectively, the “Triplet” therapy (nitisinone+sorafenib+anti-PD-1) not only achieves an excellent therapeutic effect but also has a favorable safety profile, potentially facilitating expanded access indications of nitisinone in future MSS CRC treatment strategies.2026/06/30GSE299214GSM9035226GSM9035227GSM9035228GSM9035229GSM9035230GSM903523124676299214Homo sapiens