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Cat Lady Not So Crazy After All: Cancer Breakthrough…in the Litter Box?!

By Alison Wagner, PhD, Medical Writer

kitten in litter box

To be clear, it is not the actual waste of the cat that is so intriguing (although my dog would beg to differ). It is Toxoplasma gondii (T. gondii), a parasite that requires a cat host during its lifecycle and is expelled in the feces, that has scientists from different fields, including behavioral neuroscience, immunology, and oncology, interested.

T. gondii must begin and complete its lifecycle in cats, but any warm-blooded animal can serve as an intermediate host. In these instances, the animal typically consumes the oocyst form of T. gondii. Once consumed, the oocyst ruptures and there is a brief period of fast replication and invasion of tissues (tachyzoite stage). The host’s immune response then triggers T. gondii to transform into the less active bradyzoite or chronic infection stage.
life cycle

Lifecycle of Toxoplasma gondii. (LadyofHats, Wikimedia Commons)

T. gondii is best known for giving pregnant women a great excuse to hand over litter box duties to someone else, and for good reason: first-time maternal infection with T. gondii during pregnancy can have significant effects on the developing fetus or even cause miscarriage. These effects are at least partially due to an inflammatory reaction of the maternal immune system to the parasite. People with immune deficiencies, such as HIV patients, are also at risk for complications associated with T. gondii infection, but the widespread belief until recently was that infection with T. gondii in healthy adults, though common (currently up to a third of the global population), was generally asymptomatic.

However, researchers noted that mice infected with T. gondii showed a peculiar behavior – they lost their fear response to cats (specifically, to cat odors). Causing that change in behavior is advantageous to T. gondii because the lack of fear would improve the odds that a cat could kill and eat the mouse, which in turn would perpetuate the parasite’s lifecycle. Interestingly, this effect lasted long after T. gondii had been cleared from the body, indicating that it is not a direct effect of the parasite itself. The authors of the study suggest that the immune system response that continues after the parasite is eliminated might be the culprit, rather than the actual parasite, which would explain why the behavior persists.

If T. gondii can make mice behave contrary to their natural instincts, what about humans? As it turns out, infection with T. gondii does appear to alter human behavior. For instance, infected men are said to be on average more jealous and more likely to disregard rules, while infected women are typically more warm and outgoing. T. gondii infection is also linked to an increased risk of schizophrenia, possibly due to an inflammatory response that increases release of dopamine, the key neurotransmitter known to be involved in schizophrenia.

Many media outlets immediately linked these changes to “crazy cat lady syndrome” (see here, here, here, and here). However, in my humble opinion, the behavioral changes don’t fit the stereotypical crazy cat lady. The characteristics I associate with CCLs include “introverted,” “unsocial,” and “misanthropic,” not “warm and outgoing.”

As fascinating as the effects of T. gondii on behavior are, what does that have to do with cancer and a potential new therapy? As Heather Lasseter discussed in her cancer immunotherapy post, many of the most promising cancer vaccines in development now address the problem of inhibition of normal T-cell response by molecules like CTLA-4 and PD-1 that are released by the cancer cells. And as I discussed in my last post (“Why Wolverine Will Never Get Cancer”), the immune system is intimately involved in whether cancer cells survive and thrive or not. Figuring out how to manipulate the immune system accordingly would be an enormous breakthrough in cancer therapy.

It turns out that T. gondii elicits a very specific reaction from the immune system. Rather than trying to “hide,”  T. gondii activates T cells and other inflammatory responders such as natural killer (NK) cells. This provokes the immune system to do exactly what it is supposed to do – attack invaders – and  limits the growth of T. gondii into surrounding tissue. It may seem like the worst war strategy ever for T. gondii to basically wave a flag at the enemy while shouting taunts. However, this strategy works because of the parasite’s specific lifecycle (see above) – the immune response to the invader actually aids in its transformation into bradyzoites, an essential part of that lifecycle.

Because T. gondii is so excellent at producing T-cell and NK-cell response, it can induce the exact conditions needed to stimulate the immune system and overcome the inhibitory signals from cancer cells. Indeed, researchers using a non-replicating* form of T. gondii as a basis for a cancer vaccine found that mice given this vaccine were able to achieve extraordinarily high levels of survival against extremely aggressive cancers. Immune cells in the tumor microenvironment showed higher levels of activation, indicating that the T. gondii–based vaccine had jump-started the immune system into attacking the tumor cells more aggressively and causing tumor regression. These kinds of studies have not yet been conducted in human patients – the science is still very much in the preclinical phase – but given that mice and humans are both intermediate hosts to T. gondii and show similar immune responses to the parasite, it is reasonable to anticipate positive results as this potential vaccine is tried in humans.

*The non-replicating part is key here – giving people a systemic parasitic infection is generally not considered good practice, especially when those patients are potentially immunocompromised. The vaccine that is in preclinical development is based on T. gondii, but does not produce a live infection, because a key gene for replication of T. gondii is removed.

So what does this all mean? Some might say: eat cat poop to prevent cancer. I would suggest holding off on that. It’s likely that the T. gondii (or T. gondii–like vaccine) would need to be present directly at the tumor site rather than distributed systemically; also, most indoor house cats don’t actually have T. gondii (sorry, pregnant ladies hoping to get out of litter box duty). You would then have eaten cat poop for no good reason, and that’s just disgusting. However, we can conclude that while we are making progress on understanding the immune system and how it can be a major player in cancer therapeutics, there may just be a few shortcuts we can take, provided by nature (and cat poop).

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