Some tumors do not respond to the immune system and cytotoxic cells that are naturally involved in the body’s defense. In a recent study, these unresponsive “cold” tumors were treated with immunotherapy and an inactivated protozoan in a mouse model. Results showed regression of the tumors after treatment and improved survival rates in the treated mice.
Tumor cells undergo profound genetic changes and, in particular, stop expressing antigens on their surface that trigger the immune response as the disease progresses. This allows them to escape the surveillance and destruction system of cytotoxic cells. In addition, some of them can express transmembrane proteins Programmed death ligand 1 (PD-L1) that allow them to escape cytotoxic T lymphocytes by inducing their inhibition.
Unlike chemotherapy or radiation therapy, this new method of treatment does not directly attack the cancer cells but helps the immune system recognize and destroy them. In this approach, some of the tools used, such as monoclonal antibodies (anti-PDL1), have the advantage of specifically targeting tumor cells by blocking the expression of proteins that allow them to avoid immune cytotoxicity. Long-lasting therapeutic effects have recently been demonstrated using this immunotherapy against solid tumors in advanced cancers.
Toxoplasma Gondii: a useful parasite
Because there are tumors that do not respond to immunotherapy, so-called cold tumors, a group of researchers from the Universities of Nottingham (UK) and Ningbo and Shanxi (China) came up with the idea of using inactivated pathogens such as Toxoplasma Gondii to modulate the immune response in cold tumors. The idea is to enhance the therapeutic effect of monoclonal antibodies that block the escape proteins of cancer cells.
Toxoplasma Gondii usually associated with cats (Crazy Cal Lady Syndrom) is an intracellular protozoan parasite that infects warm-blooded animals, including humans. It is found worldwide (one-third of the world’s population is considered carriers). It does not usually cause symptoms but is known to be dangerous to seronegative pregnant women (risk of fetal abnormalities) or immunocompromised individuals (cerebral toxoplasmosis). It can, if inactivated, increase immunogenicity in the tumor microenvironment and reverse tumor-related immunosuppression.
In this study, using a mouse model of cancer (melanoma, lung cancer, and colon adenocarcinoma), the researchers combined intra-tumor administration of an avirulent mutant strain of Toxoplasma Gondii with anti-PDL1 immunotherapy that targets the junction between immune cells (T lymphocytes) and proteins on the surface of tumor cells. The results showed a reduction in tumor size in the different tumors studied, provided the injection site is in the tumor microenvironment. This decrease is associated with increased infiltration of inflammatory cells with a pivotal role of CD8 and NK natural killer T cells and an improvement in the survival rate of mice.
The use of immunotherapies that block immune checkpoints developed by some cancers offers new perspectives in cancer treatment. However, the efficacy of such treatment is limited to a minority of patients. By combining this treatment with an injection of inactivated Toxoplasma Gondii into tumors, this study explores new avenues in cancer treatment research.
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