Multiomics assessment of immune-mediated melanoma cells glycocalyx remodeling for identification of novel targets in translational tumor biology

According to World Health Organization (WHO) cancer is still one of the major causes of mortality with almost 10 million deaths worldwide. Among various forms of cancer, melanoma incidence has increased since the '70s, particularly in the fair-skin population. Although immunotherapy revealed itself as one of the most attractive therapeutic options compared with chemo- and radiotherapy, particularly using immune checkpoint inhibitors (ICIs), only a subgroup of patients displays a net clinically benefit and even from these, some show relapse, developing drug-resistant tumors. This underlies the complex interaction between cancer cells and the immune system, particularly considering that immune evasion is one the cancer hallmarks. One of the major contributors to this immune evasion is the glycoconjugate complex architecture found on the outer surface plasma membrane of cancer cells, the glycocalyx, which essentially involves a proteo-glyco-lipid composition. It has been shown for example, that increase sialylation allows cancer cells to avoid immune detection. Here we would like to address the glycocalyx dynamic features which contributes to the cancer-immune cell crosstalk, by using a dedicated multi-omics workflow encompassing mass-spectrometry-based proteomics, glycoproteomics and glycolipidomics analysis. This would result in the description of novel glycoconjugates with immunomodulatory properties, valuable for the translational tumour biology field.