In a genetically-engineered mouse model of melanoma that exhibits stabilized β-catenin expression, it was first discovered that aberrant activation of this pathway could lead to the disappearance of immune cells from the tumor microenvironment (TME) and the development of tumor resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy[13,20]. The gene discussed is CTLA4; the disease is neoplasm.