A number of highly mutated cell signaling pathways are new to cholangiocarcinoma and possess immune-based functions including ADP-ribosylation factor 6 (ARF6) trafficking (FDR 0.047), Semaphorin 4D (SEMA4D) (FDR 0.047) and Rho-Roc signaling (FDR 0.049). Here, ARF6 is linked to cholangiocarcinoma.