Orphan drug nitisinone combined with sorafenib synergistically boosts anti-PD-1 efficacy in MSS Colorectal Cancer [RNA-Seq]

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.