Toxoplasma gondii-Derived Exosomes: A Potential Immunostimulant and Delivery System for Tumor Immunotherapy Superior to Toxoplasma gondii.

Abstract

Immunotherapies such as immune checkpoint blockade (ICB) therapy and chimeric antigen receptor T-cell (CAR-T) therapy have ushered in a new era of tumor treatment. However, most patients do not benefit from immunotherapy due to limitations such as narrow indications, low response rates, and high rates of adverse effects. Toxoplasma gondii (T. gondii), a specialized intracellular protozoan, can modulate host immune responses by inhibiting or stimulating cytokines. The ability of T. gondii to enhance an organism's immune response was found to have a direct anti-tumor effect and enhance the sensitivity of patients with tumors to ICB therapy. However, the application of T. gondii for tumor therapy faces several challenges, such as biosafety concerns. Exosomes, a subtype of extracellular vesicle that contains active components such as proteins, nucleic acids, and lipids, have become effective therapeutic tools for various diseases, including tumors. Parasites, such as T. gondii, mediate the communication of pathogens with immune cells and modulate host cellular immune responses through exosomes. Growing evidence indicates that T. gondii-derived exosomes mediate communication between pathogens and immune cells, modulate host immune responses, and have great potential as new tools for tumor therapy. In this review, we highlight recent advances in isolation and identification techniques, profiling analysis, host immunomodulatory mechanisms, and the role of T. gondii-derived exosomes in tumor immunotherapy. Additionally, we emphasize the potential of T. gondii-derived exosomes as delivery platform to enhance anti-tumor efficacy in combination with other therapies. This review proposes that T. gondii-derived exosomes may serve as a novel tool for tumor immunotherapy owing to their ability to activate host immune function and properties such as high modifiability, stability, and low toxicity. This work will assist in promoting the application of parasite exosomes in tumor therapy.