The tumour glyco-code as a novel immune checkpoint for immunotherapy

Could the specific glycosylation signatures associated with tumour cells be harnessed for immunotherapy purposes? In this Opinion, the authors propose that the tumour glyco-code may represent a novel immune checkpoint that could be targeted in the clinic. Tumour growth is accompanied by tumour evasion of the immune system, a process that is facilitated by immune checkpoint molecules such as programmed cell death protein 1 (PD1). However, the role of tumour glycosylation in immune evasion has mostly been overlooked, despite the fact that aberrant tumour glycosylation alters how the immune system perceives the tumour and can also induce immunosuppressive signalling through glycan-binding receptors. As such, specific glycan signatures found on tumour cells can be considered as a novel type of immune checkpoint. In parallel, glycosylation of tumour proteins generates neo-antigens that can serve as targets for tumour-specific T cells. In this Opinion article, we highlight how the tumour 'glyco-code' modifies immunity and suggest that targeting glycans could offer new therapeutic opportunities.