The Dual Role of Exosomes in the Tumor Microenvironment: From Pro‐Tumorigenic Signaling to Immune Modulation
Jiale Li, Jun Peng, Jiachong Wang, Zigui Chen
Abstract
ABSTRACT Exosomes are small extracellular vesicles that mediate intercellular communication within the tumor microenvironment. They carry a wide array of bioactive molecules, including proteins, lipids, and noncoding RNAs, and regulate critical aspects of tumor progression. Tumor‐derived exosomes influence proliferation, invasion, angiogenesis, metabolic adaptation, and resistance to therapy. They also shape the immune landscape by modulating antigen presentation, suppressing cytotoxic lymphocyte activity, and promoting the expansion of immunosuppressive cell populations. Although frequently associated with immune evasion, exosomes can also stimulate anti‐tumor immunity under specific conditions. Exosomes derived from immune cells can transfer antigenic information and cytolytic molecules, and engineered exosomes are being investigated as delivery systems for immunostimulatory agents or tumor antigens. This functional plasticity reflects the context‐dependent nature of exosomal signaling in cancer. In this Review, we provide a broad overview of exosome‐mediated regulation across cancer types. We focus on the specificity of exosomal noncoding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, which modulate both tumor behavior and immune dynamics. We also examine how exosomes affect the response to immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor T cell therapy. In addition, we highlight advances in exosome‐based diagnostics and therapeutic applications, such as their use as liquid biopsy biomarkers and as vectors for precision drug delivery. Understanding the dual roles of exosomes in cancer progression and immune modulation offers new directions for improving cancer diagnosis and therapy.