Tumor glyco-immunology, glyco-immune checkpoints and immunotherapy.

Immunotherapy, including immune checkpoint inhibition, has transformed the prognosis of many patients with cancer. However, most patients have primary or secondary resistant tumors to currently available cancer immunotherapies. Changes in glycosylation of malignant cells and in the tumor microenvironment are a new target to overcome resistance to current cancer immunotherapies and to improve the outcome of patients. Here, we summarize how changes in glycosylation in cancer have functional consequences on the immune system. Such changes can be directly targeted with drugs. Moreover, they can mediate immune-suppressive effects. For example, increased sialylation can enhance interactions with immune-inhibitory Siglec receptors, and galectin-mediated interactions can modulate immune responses in the context of cancer. Finally, we provide an overview of approaches to therapeutically target these changes for the improvement of cancer immunotherapy.