Indeed, preclinical studies using targeting innate immune cells in mouse models, suggest novel therapeutic strategies through inhibiting immunosuppressive MФs (178), activating ILC3s (216) and DCs (225), either alone or in combination with anti-PD-1/anti-CTLA-4 therapy in primary or metastatic colorectal cancer. This evidence concerns the gene PDCD1 and metastatic colorectal cancer.