A roadmap for translational cancer glycoimmunology at single cell resolution

Cancer cells can evade immune responses by exploiting inhibitory immune checkpoints. Immune checkpoint inhibitor (ICI) therapies based on anti-CTLA-4 and anti-PD-1/PD-L1 antibodies have been extensively explored over the recent years to unleash otherwise compromised anti-cancer immune responses. However, it is also well established that immune suppression is a multifactorial process involving an intricate crosstalk between cancer cells and the immune systems. The cancer glycome is emerging as a relevant source of immune checkpoints governing immunosuppressive behaviour in immune cells, paving an avenue for novel immunotherapeutic options. This review addresses the current state-of-the-art concerning the role played by glycans controlling innate and adaptive immune responses, while shedding light on available experimental models for glycoimmunology. We also emphasize the tremendous progress observed in the development of humanized models for immunology, the paramount contribution of advances in high-throughput single-cell analysis in this context, and the importance of including predictive machine learning algorithms in translational research. This may constitute an important roadmap for glycoimmunology, supporting careful adoption of models foreseeing clinical translation of fundamental glycobiology knowledge towards next generation immunotherapies.