A parasite associated with immunotherapy could improve the response of certain tumors

Some tumors do not respond to the immune system and cytotoxic cells that are naturally involved in the body’s defenses. In a recent study, these so-called “cold” tumors were treated with immunotherapy and an inactivated protozoan in a mouse model. The results show regression of the tumors after treatment and an improved survival rate in the treated mice.

The cells cancerous present profound changes genetics and in particular, as the disease progresses, they stop expressing on their surface the antigens that trigger the immune response. This allows them to escape the surveillance and destruction system of cytotoxic cells. Furthermore, they may, for some, express protein transmembraneligand PDL1 programmed death for Timed death ligand 1) allowing them to escape lymphocytes T cytotoxic inducing his inhibition.

Therefore, a new therapeutic pathway may emerge in matter cancer treatment andimmunotherapy It has boomed in the last decade. Unlike treatments with chemotherapy Where radiotherapy, this new therapeutic approach does not directly attack the cancer cell, but rather helps the immune system to recognize and destroy tumor cells. In this field of action, certain tools used, such as monoclonal antibodies (anti-PDL1) also have the advantage of specifically targeting tumor cells by blocking the expression of proteins that allow them to escape immune cytotoxicity. Long-lasting therapeutic effects have also been observed. Recently highlighted with the use of this immunotherapy about him you die solid in the case of advanced cancers.

Toxoplasma gondii: a “useful” parasite

Because there are tumors that do not respond toimmunotherapy, the so-called cold tumors, a group of researchers from the universities of Nottingham (United Kingdom) and Ningbo and Shanxi (China) conceived the idea of ​​using agents pathogens idle like Toxoplasma gondii to modulate the immune response in cold tumors. The idea is therefore to increase the therapeutic effect of monoclonal antibodies that block escape proteins from cancer cells.

Toxoplasma gondii : it is a protozoan parasite intracellular that infects warm-blooded animals, including humans. It is present throughout the world (one third of the world’s population is considered to be a carrier). It usually does not cause any symptom even if it is known to be dangerous for HIV negative pregnant women (risk ofanomalies fetal) or for immunosuppressed people (toxoplasmosis cerebral). It can, when inactive, increase theimmunogenicity of the tumor microenvironment and tumor-related reverse immunosuppression.

Immunotherapy and parasite: a combination that allows tumor regression

In this study, in a murine model of cancers (melanoma, lung carcinoma and adenocarcinoma from colon), the researchers combine intratumoral administration of a mutated avirulent strain of Toxoplasma gondii and anti-PDL1 immunotherapy, which acts at the junction between immune cells (T lymphocytes) and proteins on the surface of cancer cells. The results show a regression of the tumor size in the different types of cancers studied, as long as the injection site is in the tumor microenvironment. This regression is associated with greater infiltration of inflammatory cells with a fundamental role of CD8 and NK T cells (natural killer) and an improvement in the survival rate of mice.

The use of immunotherapies that block the immune checkpoints developed by certain tumors offers new perspectives in treatment anticancer. However, the efficacy of such treatment is limited to a minority of patients. This study combining this treatment with an injection of Toxoplasma gondii Mutated in tumors explores new avenues in the search for cancer treatments.

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