Abstract: Bacterial outer membrane vesicles (OMVs), nanosized lipid bilayer particles released by both Gram-negative and Gram-positive bacteria, are emerging as crucial mediators of host–microbe interactions in cancer biology. This review synthesizes current evidence on how OMVs modulate tumor initiation, progression, and therapeutic responses through multifaceted mechanisms aligned with the 14 hallmarks of cancer. Studies demonstrate that OMVs can either promote or inhibit neoplastic processes depending on their bacterial origin and cargo composition. Tumor-promoting OMVs enhance proliferative signaling, drive epithelial–mesenchymal transition, facilitate metastatic dissemination via barrier disruption and angiogenesis, and weaken antitumor immunity. Conversely, other OMVs exert antineoplastic effects by triggering intrinsic apoptosis, cell-cycle arrest, immunogenic cell death, and remodeling of the tumor immune microenvironment. Pre-clinical studies further highlight the translational potential of engineered OMVs as precision nano-vaccines, immunotherapeutic agents, and adjuvants that synergize with immune checkpoint blockade, chemotherapy, or photothermal therapy while minimizing systemic toxicity. Future directions could focus on mapping of OMV cargo–pathway–phenotype networks by multidisciplinary methods, programmable vesicle design using synthetic biology, and real-time microbiome-OMV monitoring in early-phase clinical trials to enable individualized onco-therapeutics. Collectively, OMVs represent a versatile platform to bidirectionally regulate oncogenesis and therapeutic responses. Exploiting their molecular plasticity through rational engineering and precision medicine frameworks would bring transformative potential for cancer prevention, diagnosis, and treatment. Keywords: bacterial outer membrane vesicles, tumor microenvironment, carcinogenesis, metastasis, immunotherapy, nanomedicine
Gu et al. (Sun,) studied this question.