Developing immunotherapies through glycosylation reprogramming to combat solid cancers

Cancer immunotherapies, including immune checkpoint inhibitors and adoptive cell transfer, have shown great efficacy and promise against hematological malignancies. However, the value of these therapies remains inconclusive in the context of solid cancers and is limited by several obstacles, including difficulty in identifying cancer-specific antigens, limited immune cell trafficking and infiltration into tumors, and the immunosuppressive effects of the tumor microenvironment. To further optimize the clinical effects of immunotherapies, many studies have focused on modifying metabolic programs, especially glycosylation, in cells. Glycosylation, which adds a diversity of carbohydrate structures (glycans) to surface molecules on virtually all cells, regulates stimulatory and inhibitory signaling pathways. Therefore, modification of key glycosylation pathways represents a logical approach for the development of new therapeutic strategies for treating solid cancers. We review how specific glycans regulate the anticancer activities of immune cells and immunosuppressive effects of cancer cells in cancer immunotherapy. In addition, we highlight T cells with NK cell properties ex vivo primed by N-glycosylation inhibitor and their advantageous functions for treatments of solid cancers.