Hope for Mesothelioma? Parasite Triggers Tumor Regression in the Lab

A parasite found in cat feces triggered tumor regression in recent animal studies in China. It is a hopeful sign that the same process might be adapted to help human mesothelioma patients, too.  

The parasite is toxoplasma gondii. It is a single-celled parasite that can only replicate inside live host cells. It is typically found in the feces of cats or in soil or water contaminated by their feces. 

It is capable of entering most cells in most warm-blooded animals. 

The goal of the new Chinese study was to determine whether toxoplasma gondii could modulate immune response in tumors. If it can, it might help immunotherapy drugs cause tumor regression in people with mesothelioma and other hard-to-treat cancers. 

How Mesothelioma Resists Tumor Regression

Malignant mesothelioma’s ability to block the immune system makes it especially hard to treat. Tumor regression is rare, even with gold standard therapies like chemotherapy.

Mesothelioma tumors release proteins that cause cancer-killing immune system cells to ignore the cancer. This allows mesothelioma to grow and spread virtually unchecked. 

But scientists are looking for ways to change the internal workings of mesothelioma cells. They hope to find a way to ‘turn off’ this strong immune response. If mesothelioma’s immune-repelling response could be toned down, tumors would be more susceptible to immune system attack. 

Immunotherapeutic drugs would also be more likely to cause tumor regression if tumors could not shield themselves. Drugs like Keytruda and Opdivo which block the protective protein PD-L1 could do more damage to mesothelioma tumors. That is the theory behind the new Chinese study.  

Making Mesothelioma Tumors “Hot” 

Chinese researchers used mice infected with melanoma, lung cancer, or colon cancer. These tumors were “cold”, meaning they had few T-cells in their microenvironment. (Mesothelioma tumors also tend to be cold tumors.)

They injected the mouse tumors with attenuated (inactive) toxoplasma gondii then treated the mice with anti-PD-L1 therapy. Then they measured the response and watched for tumor regression. 

The researchers looked for 

• changes in PD-L1 expression
• number of immune cells infiltrating the tumors
• expression of immune-related genes

“Treatment with T. gondii ΔGRA17 tachyzoites and anti-PD-L1 therapy significantly extended the survival of mice and suppressed tumor growth in preclinical mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma,” reports author Yu-Chao Zhu in the Journal for Immunotherapy of Cancer. Dr. Zhu is with Ningbo University School of Medicine in Zhejiang.

The team concludes that injecting tumors with toxoplasma gondii induced a systemic response. It made ‘cold’ tumors more sensitive to immune checkpoint inhibitors and led to tumor regression. 

It might be effective, but toxoplasma gondii is a long way from being feasible as a treatment for malignant mesothelioma. Because the parasite can only replicate  inside live tumors, there is no easy way to mass produce it for distribution.

Source:

Zhu, Yu-Chao, et al, “Synergy between Toxoplasma gondii type I ΔGRA17 immunotherapy and PD-L1 checkpoint inhibition triggers the regression of targeted and distal tumors”, November 1, 2021, Journal for ImmunoTherapy of Cancer, https://jitc.bmj.com/content/9/11/e002970