The Potential Function of <i>Toxoplasma gondii</i> in Tumour Immunotherapy

Immunotherapy has revolutionised the clinical treatment of many types of cancer, including immune checkpoint inhibitors, adoptive cell therapies, and tumour vaccines, which are capable of providing long-term clinical benefit in some patients. Nevertheless, a high degree of tumour immune heterogeneity and an ongoing immunosuppressive the tumour microenvironment (TME) remain as limitations to therapeutic outcomes, and alternative methods to stimulate antitumor immunity are necessary. Given these limitations, recent researchers has been attracted to the fact that Toxoplasma gondii and its derivatives can be considered as unconventional parasite-derived immunomodulatory vectors in cancer immunotherapy. T. gondii infection triggers strong Th1 immunity mediated on interleukin-12 (IL-12) and interferon-γ (IFN-γ), promotes dendritic cell maturation, and activates cytotoxic T cells, thus reprogramming the TME to a more immunostimulatory condition. Attenuated or metabolic-deficient strains have shown strong antitumor efficacy in various murine tumour models by reducing tumour burden and prolonging host survival. Meanwhile, the effector proteins of the parasite, such as GRA15, GRA16, and ROP18, regulate immune cell function to induce tumour cell apoptosis, inhibit angiogenesis, and suppress metastasis. The T. gondii-infected cell-derived exosomes and T. gondii lysate antigens are also immunogenic and represent safer, non-infectious therapeutic alternatives. Here, we summarise the latest advances in the antitumor effects of T. gondii and its derivatives, focusing on immune activation, signalling regulation, direct antitumor effects, synergistic immunotherapy, potential for drug development, and challenges in future clinical translation. T. gondii and its derivatives have shown the potential to reshape TME and convert 'cold' tumours into 'hot' ones in murine cancer models. We believe that with further research in this field, the future of cancer immunotherapy will see breakthrough advancements.