Immature protein O-glycosylation, characterized by the Tn antigen expression rather than complex glycans, is prevalent in advanced solid tumors and promotes immune evasion. We developed GlycoAvatars, magnetic beads coated with plasma-membrane glycoproteins from glycoengineered cancer cells reflecting these alterations, to identify cancer-immune cell interactomes. We uncovered numerous membrane and intracellular proteins involved in glycan-mediated immune signaling, providing a novel high-throughput strategy for identifying potential relevant molecular nodes foreseeing therapeutic targets. GlycoAvatars profile glycan-dependent cancer immune membrane interfaces shaped by immature protein O-glycosylation, revealing candidate signaling networks and molecular targets that contribute to immune modulation. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give... [797 chars]