Researchers say they have identified the specific proteins secreted by the parasite Toxoplasma gondii that cause the immune system in mice to attack established ovarian tumors. The study (“Secretion of Rhoptry and Dense Granule Effector Proteins by Nonreplicating Toxoplasma gondii Uracil Auxotrophs Controls the Development of Antitumor Immunity”), led by David Bzik, Ph.D., of the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, is published in PLOS Genetics.

One promising strategy in the fight against cancer is to use the body's own immune system to remove tumor cells, but due to a phenomenon called immune tolerance, the immune system has a difficult time identifying which cells to attack. In the new study, scientists built upon previous discoveries that a safe, nonreproducing vaccine strain of T. gondii could cure mice of several types of solid tumors and identified which parasite proteins and which immunological pathways are required to break immune tolerance. They systematically deleted genes for secreted effector proteins—molecules that the parasite injects into a host cell to modulate the immune system during infection—and injected the altered parasites into mice with aggressive ovarian cancer.

Their results demonstrate that specific rhoptry (a specialized protozoan secretory organelle) and dense granule effector proteins that T. gondii secretes before and after host cell invasion, respectively, control the development of an effective host antitumor response and increase the survival of mice with ovarian tumors.

The investigators wrote, “…tracking and understanding the host cell pathways manipulated by these T. gondii secreted effector proteins can reveal fundamental mechanisms controlling immunity to infection and can also identify relevant mammalian cell mechanisms as new targets for devising more effective therapies against highly aggressive solid tumors.” 

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