Immune cell-derived exosomes in cancer: double-edged mechanisms of antitumor immunity and tumor progression

Immune cell-derived exosomes are important mediators of intercellular communication within the tumor microenvironment. Their biological effects are influenced by the immune-cell source and activation state, vesicular cargo, recipient-cell type, and tumor context. This review examines immune cell-derived exosomes as bidirectional regulators of cancer-associated signaling, with emphasis on their antitumor and protumor mechanisms rather than classification by parent cell type alone. Antitumor exosomes can enhance antigen presentation, activate natural killer cell and T-cell responses, reprogram tumor-associated macrophages, reduce immune-checkpoint signaling, induce tumor-cell death, and suppress tumor growth and metastasis. Conversely, exosomes released by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and other immune populations may promote immune suppression, tolerogenic reprogramming, checkpoint-mediated immune escape, invasion, metastasis, and treatment resistance. These effects are mediated through the transfer of proteins, receptors, enzymes, cytokine-related molecules, microRNAs, long non-coding RNAs, and other regulatory cargo that modulate signaling networks such as NF-κB, MAPK/ERK, PI3K-AKT-mTOR, STAT3, PD-1/PD-L1, apoptotic, and β-catenin/HIF-1α-associated pathways. Despite their therapeutic and diagnostic potential, clinical translation remains limited by extracellular-vesicle heterogeneity, incomplete identification of functional cargo, inconsistent isolation and characterization methods, manufacturing challenges, storage instability, and difficulties in tracking vesicles in vivo . Future studies should aim to define the relationships among parent-cell state, exosomal cargo, recipient-cell identity, and downstream biological responses. Additionally, integrating experimental data with computational and artificial-intelligence-based approaches may support single-vesicle classification, inference of EV cellular origin, and the development of more reproducible exosome-based cancer therapies.