A Glyco-Immune Checkpoint: Modulation Of The Immune Micro-Environment And Induction Of Stem Cell-Like Properties In Breast Cancer Cells.

e15104Background: Many tumors, including breast cancers, contain infiltrating immune cells that are unable to eliminate the tumor and in many cases, promote tumor progression by adding to the permissive local environment. Tumors have developed a plethora of mechanisms to evade the immune response, including inducing the expression of checkpoint ligands. Siglecs constitute a family of sialic acid binding lectins expressed on immune cells where they are involved in negatively regulating the immune response and like PD-1 contain an ITIM motif in their cytoplasmic tail. Cancers increase their surface sialylation and engage these inhibitory siglecs, mimicking some pathogens, to elicit immune evasion. As a result, siglecs and their interacting glycoproteins on tumor cells have recently been described as important glyco-immune checkpoints. Methods: Primary monocytes from healthy volunteers and macrophages differentiated from these cells were treated with recombinant MUC1 carrying the tumor-associated, sialylated...