A lipidomics approach demonstrated that the upregulation of sphingomyelin phosphodiesterase 3 by sphingomyelinase 2 (nSMase2) is a potential strategy to overcome resistance against PD-1 inhibitors according to increased PD-1 inhibitor efficacy following over-expression of wild-type nSMase2 in melanoma [88]. This evidence concerns the gene PDCD1 and melanoma.