Thus, our results support a model in which IκBζ-mediated recruitment of EZH2 and HDAC3 represses Cxcl10, Cxcl9, and Ccl5 in melanoma, contributing to the observed lack of T-cell infiltration and immunotherapy resistance in the α-PD-1-treated, IκBζ-expressing melanoma mouse models. Here, CCL5 is linked to melanoma.