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

Abstract

Lai-Xi Zhao,1,* Qiong Sun,2,* Chong Wang,3,* Jia-Jia Liu,1 Xiao-Rong Yan,1 Meng-Ci Shao,1 Li Yu,3 Wen-Hua Xu,1 Rui Xu1 1College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, 230032, People’s Republic of China; 2Department of Stomatology, Anhui Province Direct Subordinate Hospital, Hefei, 230601, People’s Republic of China; 3Department of Microbiology and Parasitology, School of Basic Medical Sciences, Anhui Medical University, Anhui Province Key Laboratory of Zoonoses, The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Hefei, Anhui Province, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen-Hua Xu; Rui Xu, Email [email protected]; [email protected]: 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. Keywords: Toxoplasma gondii, exosomes, tumor, immune regulation, immunotherapy

Keywords

• toxoplasma gondii
• exosomes
• tumor
• immune regulation
• immunotherapy