Thu. Dec 8th, 2022

By KIM BELLARD

Joe Biden hates cancer.  He led the Cancer Moonshot in the Obama Administration, and, as President, he reignited it, vowing to cut death rates in half over the next 25 years.  Last month, on the 60th anniversary of President Kennedy’s historic call for an actual moonshot, he vowed “to end cancer as we know it. And even cure cancers once and for all.”

But, as several recent studies show, cancer is still surprising us. 

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Our body has its own defenses against cancer, such as T-cells, and great strides have been made in cancer therapies, including immunotherapies.  Still, though, as first author of a new study from Tel Aviv University, Amit Gutwillig, pointed out: “Despite its remarkable success, the majority of patients who receive immunotherapy will see their tumors only shrinking in size temporarily before returning, and these relapsed tumors will likely be resistant to immunotherapy treatment.”  

One reason, it turns out, is that some cancer cells have learned to hide – in other cancer cells.

The research found: “While the outer cells in this cell-in-cell formation are often killed by reactive T cells, the inner cells remain intact and disseminate into single tumor cells once T cells are no longer present.”  Sneaky little bastards.  Or, as Professor Yaron Carmi, who heads the lab, told The New York Times, “It was like seeing the devil.”

This is groundbreaking stuff.  The authors conclude:

Overall, the ability of tumor cells to transiently enter and disseminate from each other in response to T-cell killing is a biological process that has never been described heretofore. It better explains how immunogenic tumors can survive in the host and provides a novel framework for immunotherapies

This may point to the need for new approaches.  Dr. Carmi believes:

This previously unknown mechanism of tumor resistance highlights a current limitation of immunotherapy.  Over the past decade, many clinical studies have used immunotherapy followed by chemotherapy – but our findings suggest that timed inhibition of relevant signaling pathways needs to occur alongside immunotherapy to prevent the tumor becoming resistant to subsequent treatments.

As interesting as the findings are, the NYT article suggests caution: “it remains to be seen whether it will lead to improvements in the treatment of cancer patients.”

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The next set of studies are, if anything, even more startling.  It turns out that cancer has a microbiome.  And a mycobiome.  Cancer tumors are filled with microbes, particularly fungi. 

Two studies published in Cell last week document the presence of fungi in cancer tumors. The first study looked at 35 types of cancers – and found fungi, in varying degrees, in all of them.  In many cases, they were coexisting with bacterial colonies (the presence of bacteria in cancer tumors had already been uncovered in the past five years).

First author Lian Narunsky Haziza, of the Weizmann Institute of Science in Israel, told the NYT: “I think this is an ecosystem.  It means the cancer cells are not alone.”

It’s not so much there are huge amounts of fungi present, but as STAT put it, “why are they there? And how did they get there?”  Amit Bhatt, a professor at Stanford who was not involved with either study, told STAT; “Or maybe there are immune cells that ate fungi and carried sequences to a tumor site.  Or maybe since you have a trillion microbes in and on you, it’s just not surprising that every now and then one makes its way into the body.” 

However they got there, Illana Livyatan, one of the researchers, notes: “Fungi can be food for bacteria and vice versa. They can even live within bacteria or bacteria can live within fungi. They can do a lot of biochemistry. Any of those avenues might have an effect.” 

A second study, looked specifically at fungi in gastrointestinal, lung, and breast cancers, and its findings suggest that presence of certain kinds of fungi are correlated with lower survival rates.   It’s not clear why.  The NYT article notes: “It’s possible that some microbes don’t just take up residence in tumors but help them grow. They may cloak the tumor from the immune system, neutralize drugs or help tumors spread through the body.”

Deepak Saxena, a microbial ecologist at New York University who was not involved in either study, told Nature that “more work is needed to understand whether fungi can contribute to cancer progression by causing inflammation, for example, or if advanced tumors create a habitable environment that encourages fungal cells to take hold.”

Dr. Saxena also told the NYT: “I was not expecting this amount of fungus in cancer.  This will change the way we think about it.”  Dr, Bhatt concurs, telling Stat: “We don’t have the experiments to present a causal link between tumor initiation or progression and fungi. But this really encourages future research to think about designing experiments with microbiome and mycobiome investigations in mind.”

Co-corresponding author Ravid Straussman, MD, PhD, from the Weizmann Institute of Science, added: “The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens.”

Dr. Livyatan is optimistic about the potential applications, telling The Times of Israel: “This could offer a new avenue for diagnosis of cancers using a simple blood test that detects fungi in tumors. And beyond diagnostics, this could really shake things up in tumor research. This is one of these eye-opening moments that makes us revisit our assumptions about cancer, as fungi now represent a whole new consideration in analyzing tumors.”

We’ve only been scratching the surface at understanding the presence of our microbiome/mycobiome, much less its effect on our health, so to just now realize that we need to look at cancer through that same “lens” just illustrates how far we most likely are from “ending cancer.” 

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Cancer cells hiding in other cancer cells, cancer cells cohabiting with fungi and bacteria; who knows what else there is left to surprise us about cancer (and other illnesses)? It’s an admirable goal that President Biden wants to end cancer “as we know it;” the problem is, we may not really know it all that well yet.

Kim is a former marketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor.



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