Review Article

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

Toxoplasma gondii comme médicament pour l’immunothérapie antitumorale : mécanismes, défis et perspectives

¹ School of Basic Medicine and Forensic Medicine, Zhejiang Key Laboratory of Biosafety and Biomedical Translation, Zhejiang Industrial Technology Engineering Center for Novel Vaccines, Hangzhou Medical College, Xihu District, Hangzhou 310013, PR China
² Parasitology and Animal Diseases Department, Veterinary Research Institute, National Research Centre, Dokki, Giza 126, Egypt
³ College of Medical laboratory Techniques, Al-Farahidi University, Baghdad 1001, Iraq
⁴ National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory for Parasitology and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Centre for International Research on Tropical Diseases, 207 Ruijin 2nd Road, Huangpu District, Shanghai 200025, PR China
⁵ Hainan Tropical Diseases Research Center (Hainan Sub-Center, Chinese Center for Tropical Diseases Research), Longhua District, Haikou 570203, PR China

^* Corresponding authors: This email address is being protected from spambots. You need JavaScript enabled to view it. (Shao-Hong Lu); This email address is being protected from spambots. You need JavaScript enabled to view it. (Xiao-Nong Zhou); This email address is being protected from spambots. You need JavaScript enabled to view it. (Bin Zheng)

Received: 4 September 2025
Accepted: 9 January 2026

Abstract

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.

Résumé

Toxoplasma gondii est un protozoaire parasite intracellulaire connu pour infecter un large éventail d’hôtes, y compris l’homme, et constitue une cause importante de problèmes de santé, notamment chez les femmes enceintes et les personnes immunodéprimées. Cependant, son potentiel dans le traitement du cancer, grâce à ses divers mécanismes d’action anticancéreux, suscite un intérêt croissant. Toxoplasma gondii induit la production de cytokines clés telles que l’IL-12 et l’IFN-γ, déclenchant de fortes réponses immunitaires Th1 qui ciblent efficacement les cellules tumorales. De plus, il module le microenvironnement tumoral immunosuppresseur (TME), réduit le nombre de cellules immunitaires inhibitrices, favorise l’activation des cellules immunitaires, induit l’apoptose des cellules tumorales, inhibe la prolifération et perturbe l’angiogenèse tumorale par le biais de voies de signalisation régulatrices. Malgré ces propriétés antitumorales prometteuses, d’importantes limitations entravent son application clinique. Ces difficultés incluent des différences de virulence et d’efficacité thérapeutique selon les souches, des préoccupations éthiques et de biosécurité liées aux souches sauvages, une applicabilité limitée des données animales à la thérapie humaine et la possibilité que le parasite favorise la tumorigénèse dans certaines conditions. Des approches innovantes, telles que des souches modifiées pour un ciblage tumoral précis, l’exploitation de ses agents bioactifs, son utilisation comme vecteur de médicaments pour les tumeurs cérébrales et les thérapies combinées avec d’autres modalités anticancéreuses, sont prometteuses. Ces avancées, associées à des évaluations complètes du rapport coût-efficacité, offrent de nouvelles perspectives et un espoir pour l’intégration de T. gondii dans le traitement du cancer.