Tiny extracellular vesicles known as exosomes are emerging as key regulators of the tumor microenvironment (TME), influencing how cancer progresses, spreads, and responds to treatment. In a new review published in Med Research, researchers from Haikou Affiliated Hospital of Central South University Xiangya School of Medicine explore the dual nature of exosomes—highlighting their roles in both tumor promotion and immune modulation.
"Exosomes are not just passive carriers," said Dr. Jiachong Wang, co-corresponding author of the paper. "They actively shape tumor biology by transferring RNAs, proteins, and lipids that reprogram both cancer and immune cells."
The review focuses on tumor-derived exosomes (TDEs) and their diverse molecular cargo, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), which contribute to oncogenesis. These exosomes promote tumor cell proliferation, angiogenesis, metastasis, and drug resistance by activating key signaling pathways—including PI3K/AKT, MAPK/ERK, Wnt/β-catenin, and NF-κB.
At the same time, TDEs also profoundly influence the immune landscape. They can suppress immune responses by delivering immunoinhibitory ligands like PD-L1 and CTLA-4 or by inducing immunosuppressive cell types, such as M2 macrophages and regulatory T cells. Conversely, exosomes from immune or engineered cells may restore antitumor immunity by delivering cytokines, antigenic peptides, or RNA-based therapeutics.
The review also discusses liquid biopsy applications, showing how exosomal RNA and protein content reflects tumor stage, heterogeneity, and treatment response. This paves the way for noninvasive monitoring of disease progression and therapy resistance.
As interest in exosome biology grows, this review synthesizes current knowledge while pointing to future directions, such as exosome engineering and combined immunotherapy approaches. It positions exosomes as both culprits and potential cures in the evolving fight against cancer.
