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  • Role of PDEV in Cancer Immunotherapy

  • Mohadeseh Shayeghan,1 Esmaeil Babaei ,2 Mohammad Amin Javidi,3,*
    1. Department of Animal Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran
    3. Integrative Oncology Department , Breast Cancer Research Center , ACECR , National Cancer Institute , Tehran , Iran


  • Introduction: Plant-derived extracellular vesicles (PDEVs) have attracted considerable attention as natural bioactive nanovesicles with potential applications in cancer therapy. Containing diverse bioactive molecules, including lipids, proteins, RNAs, and plant-derived compounds, PDEVs may exert intrinsic biological effects by modulating cellular pathways and immune responses involved in tumor progression. Their inherent biocompatibility, low immunogenicity, stability, and low toxicity further support their potential as natural therapeutic agents. Therefore, PDEVs represent promising candidates for the development of novel plant-based anticancer treatment.
  • Methods: Related articles were selected from databases like PubMed, Scopus, ScienceDirect, and Google Scholar with the following keywords: Herbal Medicine, Plant-Derived Extracellular Vesicles, Cancer Treatment, Immunotherapy.
  • Results: The role of PDEVs in cancer immunotherapy is primarily linked to their ability to modulate anti-tumor immune responses. Importantly, PDEVs are not merely drug carriers; owing to their bioactive plant compounds, they can directly influence cellular interactions and pathways associated with the immune response. One of the key mechanisms of PDEVs is their influence on macrophage polarization, shifting cells from an M2-like to an M1-like phenotype. M1 macrophages are associated with anti-tumor activity and the production of inflammatory factors. For instance, ginseng-derived nanovesicles (GDNVs) induce M1-like macrophage polarization through the activation of the TLR4/MyD88 pathway and increase the production of reactive oxygen species (ROS). This process can induce apoptosis in melanoma cells. GDNVs can stimulate tumor-associated macrophages (TAMs) to secrete increased levels of the chemokines CCL5 and CXCL9. These chemokines promote the recruitment of CD8+ T cells to the tumor site and can enhance the anti-tumor immune response. According to a literature, GDNVs demonstrated a synergistic effect with anti-PD-1 monoclonal antibodies by enhancing the infiltration of CD8+ T cells into tumor tissue. This finding suggests that PDNVs could potentially be used alongside immune checkpoint inhibitors to boost anti-tumor immunity. PDEVs can also alter the tumor microenvironment by affecting tumor-associated macrophages and inhibiting the growth of cancer-associated fibroblasts (CAFs). These changes can play a role in regulating the immune response and limiting tumor progression.
  • Conclusion: Compared with conventional plant extracts, PDEVs offer a naturally organized and stable structure that can encapsulate and protect bioactive plant compounds. This vesicular organization may improve the stability, cellular uptake, and bioavailability of these bioactive components compared with their free forms. In addition, PDEVs can facilitate the interaction of plant-derived molecules with recipient cells through their lipid bilayer and nanoscale characteristics. Therefore, PDEVs provide not only the biological activities associated with their plant-derived cargo but also a natural nanoscale platform that may enhance the delivery and therapeutic potential of these compounds. Importantly, the immunological effects of PDEVs should not be generalized across all plant species or vesicle preparations. The biological activity of PDEVs is likely influenced by their plant source, molecular composition, isolation method, and interactions with specific recipient cells. Therefore, identifying the bioactive components responsible for immunomodulation and establishing standardized methods for PDEV isolation and characterization are essential for advancing their therapeutic development. In addition, further studies are required to clarify their biodistribution, cellular uptake, long-term safety, and potential effects on systemic immune responses. Overall, the available evidence supports the concept that PDEVs can function as biologically active mediators of tumor–immune interactions rather than merely serving as passive nanocarriers. Their ability to regulate macrophage polarization, enhance chemokine-mediated CD8+ T-cell recruitment, influence the tumor microenvironment, and potentially cooperate with immune checkpoint inhibition highlights their potential as a novel plant-derived approach to cancer immunotherapy. In conclusion, PDEVs show considerable potential as biologically active components of future cancer immunotherapy although their clinical efficacy and safety require more validation.
  • Keywords: Herbal Medicine, Plant-Derived Extracellular Vesicles, Cancer Treatment, Immunotherapy.

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