<i>Toxoplasma gondii</i> as a drug for anti-tumor immunotherapy: mechanisms, challenges, and perspectives

Toxoplasma gondii is an intracellular protozoan parasite known to infect a wide range of hosts, including humans, and is a significant cause of health issues, particularly in pregnant women and immunocompromised individuals. However, it has garnered attention for its potential in cancer treatment due to its diverse anti-cancer mechanisms. Toxoplasma gondii induces key cytokines such as IL-12 and IFN-γ, triggering robust Th1 immune responses that effectively target tumor cells. Furthermore, it modulates the immunosuppressive tumor microenvironment (TME), reduces inhibitory immune cells, promotes activated immune cells, induces apoptosis in tumor cells, inhibits proliferation, and disrupts tumor angiogenesis through regulatory signaling pathways. Despite these promising antitumor attributes, significant limitations hinder its translation into clinical practice. These include strain-dependent differences in virulence and therapeutic efficacy, ethical and biosafety concerns associated with wild-type strains, limited applicability of animal data to human therapy, and the possibility that the parasite may promote tumorigenesis under certain conditions. Innovative approaches such as engineered strains for precise tumor targeting, exploitation of its bioactive agents, use as a drug carrier for brain tumors, and combination therapies with other anti-cancer modalities show promise. These advances, coupled with comprehensive cost-effectiveness assessments, present new opportunities and hope for integrating T. gondii into cancer therapy.