However, the rationale behind the decrease abundance of T-regs in LvM is poorly understood, as in other primary cancers such as hepatocellular carcinoma, metastatic colorectal and prostate cancer to the liver, there have been reported to be higher numbers of T-regs in the liver and associated genes such as LAG3, GITR, ICOS, and CTLA-4, which have correlated with worse outcomes [40–42]. This evidence concerns the gene ICOS and cancer.