Toxoplasma Parasite Improves Response to Checkpoint Blockade Immunotherapy in Mice

Toxoplasma Parasite Improves Response to Checkpoint Blockade Immunotherapy in Mice

A new study has revealed the protozoan parasite, Toxoplasma gondii, which causes toxoplasmosis in humans and mammals, could prove to be hugely beneficial to cancer patients.

Toxoplasmosis is a potentially harmful illness if the parasite infects immunocompromised patients or pregnant women; however, most people do not develop any symptoms or, at worst, develop flu-like symptoms.

A team of researchers from the University of Nottingham, Ningbo University, and Shanxi Agricultural University has shown injecting tumors with the parasite improves the effectiveness of checkpoint inhibition therapy.

The study was conducted to determine whether modulation of the immune response by T.gondii within tumors would sensitize the tumors to checkpoint blockade immunotherapy.

The researchers first developed a mutant T.gondii strain with a reduced ability to grow in cultured cells and had a reduced capability to cause disease in mice, but was still able to manipulate the host immune system. The researchers injected the mutant T.gondii strain into solid tumors in mice and found an inflammatory response in the tumors, and even in tumors in a distant location in from the injection site.

When mice were treated with immune checkpoint inhibitors, the mice that had been injected with the mutant T.gondii strain responded better to treatment than the control group, extending survival and reducing tumor growth in mouse models of several cancers, including Lewis lung carcinoma, colon adenocarcinoma, and melanoma.

The researchers report attenuation of tumor growth in the injected and distant tumors, which was associated with upregulation of innate and adaptive immune pathways, with complete regression of tumors underpinned by late interferon-gamma-producing CD8+ cytotoxic T cells.

“The use of a mutant version of T. gondii in the treatment of certain tumors in mice models has been previously reported. What makes this study different is the confirmation that intratumoral injection with mutant T. gondii strain boosts antitumor immunity and the effectiveness of checkpoint inhibition therapy,” said Hany Elsheikha, PhD, of the University of Nottingham. “The marked reduction in tumor size and the significant improvement in the survival of mice that received this novel combinational therapy is promising but should be interpreted with caution as further research is needed.”

You can read more about the study in the paper – Synergy between Toxoplasma gondii type I ΔGRA17 immunotherapy and PD-L1 checkpoint inhibition triggers the regression of targeted and distal tumors – which was recently published in the Journal for ImmunoTherapy of Cancer. DOI: 10.1136/jitc-2021-002970