The treatment of mice with xCT inhibitor or the genetic deletion of xCT significantly inhibited melanoma cell proliferation, however, the combination of xCT inhibition and anti-PD-1/PD-L1 therapy reduced the efficacy of anti-PD-1/anti-PD-L1 treatment in melanoma by impairing the cytotoxicity of CD8+ T cells and inducing M2 macrophage polarization. Here, CD8A is linked to melanoma.