Extracellular vesicles in colorectal cancer: immunomodulation, diagnostics, and therapeutic perspectives.

Colorectal cancer (CRC) remains a significant global health concern and is among the leading causes of cancer-related mortality. The disease often progresses to more advanced and treatment-resistant stages. By 2040, the incidence of CRC is projected to increase substantially worldwide, particularly in low- and middle-income countries. Despite the availability of various treatment modalities, CRC incidence remains elevated. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, represent a novel approach for CRC therapy and diagnosis. EVs possess distinct biological characteristics and exhibit both immunosuppressive and immunostimulatory properties within the tumour microenvironment. Tumour-derived EVs facilitate CRC progression and metastasis by transferring oncogenic proteins and microRNAs that promote epithelial-mesenchymal transition and alter recipient cell behaviour. Conversely, immune-derived EVs produced by dendritic cells, natural killer cells, T lymphocytes, B lymphocytes, and macrophages enhance anti-tumour immune responses and contribute to the elimination of cancer cells. Due to their stable encapsulation of nucleic acids, proteins, and lipids, EVs serve as highly sensitive and specific biomarkers for CRC diagnosis, prognosis, and therapeutic monitoring. Additionally, EVs have demonstrated both abscopal and bystander effects, highlighting their capacity to induce systemic antitumor responses. Recent advances in EV engineering, together with emerging technologies such as artificial intelligence, CRISPR/Cas9 genome editing, and chimeric antigen receptor (CAR)-T cell therapy, present new opportunities to optimise EV-based interventions and broaden their translational applications. Nevertheless, substantial challenges persist, including EV heterogeneity, technical barriers in isolation and characterisation, and limited understanding of their functional diversity. Addressing these limitations, particularly in the development of EV-based vaccines, enhancement of immunostimulatory properties, and further integration of artificial intelligence, will be essential for realising the full clinical potential of EVs in colorectal cancer management.