Advanced cutaneous melanoma can be treated by immunotherapy targeting immune check points such as PD-1 and CTL-A4. However, 50% of patients do no respond because of primary or acquired resistance mechanism. Thus, new targets for addressing the treatment of said resistance are highly needed. The inventors show that TNF (Tumour Necrosis Factor) and ceramide metabolism alterations in melanoma cells contribute to melanoma progression and resistance to immunotherapies. In particular, the inventors demonstrate that TNF is a potent modulator of ceramide metabolism and TNF-mediated ceramide metabolism changes contribute to various biological processes such as cell proliferation, cell death and cell differentiation. Among the biological processes by which TNF triggers melanoma immune escape and resistance to immunotherapies, TNF triggers a dedifferentiation process of melanoma cells associated with the reduction of melanocytic antigen expression and epithelial to mesenchymal transition. Finally, the inventors show that glycosphingolipid pattern in plasma can predict the clinical outcome of advanced melanoma treated with ipilimumab and nivolumab. Accordingly, ceramide metabolites and metabolizing-enzymes can be new therapeutic targets and/or biomarkers in advanced melanoma patients treated with immunotherapies.