Exosomal nanocarriers of immune fate: molecular insights into cancer immunity, pathogen defense, and emerging immunotherapies

Exosomes, the nanoscale extracellular vesicles released by most cell types, are increasingly recognized as potent regulators of immune communication. This review provides a mechanistic and integrative perspective on the immunological functions of exosomes, highlighting their roles in both immune stimulation and suppression across physiological and pathological contexts. We begin by dissecting the molecular architecture of exosomes-focusing on immunologically active components such as ESCRT proteins, tetraspanins, RabGTPases, and lipid mediators-and explore how these elements contribute to exosome biogenesis and immune function. The review further examines exosomal cargo enriched in pattern recognition receptor (PRR) ligands, including damage-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), and microRNAs, and discusses how these molecules activate toll-like receptors and other PRRs to orchestrate innate immune responses through endosomal and cytosolic signaling cascades. Special emphasis is given to MHC-mediated antigen presentation via exosomes, distinguishing classical and non-canonical pathways and their interplay with downstream immune signaling mechanisms. We present a dichotomous view of exosomes as both immunostimulatory and immunosuppressive agents, detailing their roles in T-cell cross-priming, dendritic cell maturation, tumor progression, and metastasis. Moreover, we review pathogen-driven hijacking of exosomal pathways and their implications for immune evasion. Finally, we discuss the therapeutic promise of exosomes in cancer immunotherapy and vaccine design, advocating for their strategic integration into next-generation immunomodulatory approaches.