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.