Role of cancer cell-derived exosomal glycoproteins in macrophage polarization

Abstract

Cancer is a deadly disease marked by abnormal cell growth, proliferation, and metastasis—the spread of cancer from its origin to distant sites. A key factor in tumor progression is the tumor microenvironment (TME), which significantly influences tumor behavior and response to treatment. Within the TME, interactions between cancer cells and surrounding immune cells, particularly tumor-associated macrophages (TAMs), play a critical role in shaping immune responses. This review focuses on recent findings from a systematic PubMed search regarding cancer cell-derived exosomal glycoproteins and their role in modulating macrophage phenotypes. Tumor-derived exosomes, a type of extracellular vesicle (EV), carry glycoproteins—proteins with attached sugar chains—that can influence macrophage polarization. These glycoproteins can reprogram macrophages into either the M1 phenotype (proinflammatory and anti-tumor) or the M2 phenotype (anti-inflammatory and tumor-supportive). The M1 macrophages inhibit tumor progression, while M2 macrophages support tumor growth by promoting immune suppression and tissue remodeling. Understanding how exosomal glycoproteins drive this polarization offers critical insight into cancer immunology and may pave the way for novel therapeutic strategies targeting the TME. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.