The sialoglycan-Siglec glyco-immune checkpoint - a target for improving innate and adaptive anti-cancer immunity

Abstract

Introduction: During cancer progression, tumor cells develop several mechanisms to prevent killing and to shape the immune system into a tumor-promoting environment. One of such regulatory mechanism is the overexpression of sialic acid (Sia) on carbohydrates of proteins and lipids on tumor cells. Sia-containing glycans or sialoglycans were shown to inhibit immune effector functions of NK cells and T cells by engaging inhibitory Siglec receptors on the surface of these cells. They can also modulate the differentiation of myeloid cells into tumor-promoting M2 macrophages. Areas covered: We review the role of sialoglycans in cancer and introduce the Siglecs, their expression on different immune cells and their interaction with cancer-associated sialoglycans. The targeting of this sialoglycan-Siglec glyco-immune checkpoint is discussed along with potential therapeutic approaches. Pubmed was searched for publications on Siglecs, sialic acid, and cancer. Expert opinion: The targeting of sialoglycan-Siglec interactions has become a major focus in cancer research. New approaches have been developed that directly target sialic acids in tumor lesions. Targeted sialidases that cleave sialic acid specifically in the tumor, have already shown efficacy; efforts targeting the sialoglycan-Siglec pathway for improvement of CAR T cell therapy are ongoing. The sialoglycan-Siglec immune checkpoint is a promising new target for cancer immunotherapy.

Keywords: Immune checkpoint; NK cell; T cell; sialic acid; tumor-associated macrophage.