CTLA4 and melanoma: In mouse melanoma models, intrinsic β-catenin activity within tumors has been shown to exclude T cells and confer resistance to PD-L1/anti-CTLA-4 monoclonal antibody therapy.375 Furthermore, analysis of primary BRAF-mutant melanoma revealed a negative correlation between T cell infiltration and β-catenin levels in tumor cells.689 The Wnt3a-β-catenin signaling cascade depletes tumor-infiltrating T cells, reducing their antitumor activity and inhibiting the generation of effector memory T cells.690