The bacteria in cancer

Back in 2017, Chris Smith spoke with Israeli scientist Ravid Straussman. Looking at pancreatic cancer samples, he'd stumbled on the surprising observation that the majority of the cancerous cells he looked at had bacteria lurking inside them. These microbes appeared to be helping the cancer cells to survive and even defending them from chemotherapy drugs. Knocking out these bacteria might therefore be an additional way to target cancer cells, or at least sensitise them to some anti-cancer drugs. But is it just pancreatic cancer that does this? In a new study from the Weizmann Institute in Israel, published in Science, by widening the search, it looks like the answer is no, as Chris has been finding out...

Ravid - A few years ago, we found almost incidentally that inside human pancreatic cancer - so inside these tumours - one can find bacteria. We're also able to show that these bacteria can protect cancer cells from chemotherapy, we found that these bacteria can inactivate the chemotherapy. So our challenge here was, we wanted to know if this is a more general thing. Can we find bacteria in many different tumour types? So what we did was we took biopsies or tumours from 1500 cancer patients. These included breast cancer, bone cancer, pancreatic cancer, brain cancer, ovarian cancer, lung cancer, skin cancers. And we were surprised to see that in each one of these cancer types, we could find bacteria. We found that in every cancer type there seems to be different bacteria. So you kind of find the same bacteria in different patients, let's say with breast cancer; but the bacteria that are present in patients with breast cancer are very different from the one that you find in lung cancer or other cancer types.

Chris - Do you think these bacteria are viable? It's not just that the tumour cells are being like a giant sieve and the bacteria that naturally go around the bloodstream anyway, they're getting grabbed in a deactivated or dead state and just pulled into these cancer cells, 'cause they're abnormal cells. Are these live, viable bacteria?

Ravid - For sure these bacteria are viable. We were able to grow live bacteria from these tumours.

Chris - What comes first then? Does the tumour develop and then it recruits these bacteria from somewhere, or do you think the bacteria settle in tissue that's destined to become a cancer and the two co-evolve?

Ravid - We don't have good enough data to answer that for all these cancer types. My bet is that both of them can be true. It's been known for many years that some viruses, as well as some bacteria, can contribute to the transformation process - meaning transforming normal cells to cancer cells. But it can be the case, as you mentioned, that you have some tumours; and after you have these tumours, bacteria find refuge in them. So we're not sure yet which comes for us in the process of tumourigenesis.

Chris - It's not just a random process though, is it? Because you're seeing these very similar types of bacteria that crop up time and again in the same sorts of tumours, and they're quite different from other sorts of tumours; which suggests there's some kind of control going on, something is determining whether that's coming from the bacteria selecting their host tumour or the tumour selecting their bacteria they want to give a home to. Something is guiding that process.

Ravid - Absolutely. A nice glimpse that we had into this process is probably coming from lung cancer. We looked at lung tumours from smokers and patients that never smoked before. And when we compared the bacteria inside tumours coming from the lungs of smokers and nonsmokers, we saw some bacteria that are very specific only to the smokers. And then we looked into the genes that are found inside these bacteria. What we found is enrichment of genes that can degrade chemicals that are found in cigarette smoke; for example, nicotine or other chemicals. So what we reason is that patients who smoke have all these smoke-related chemicals in their lungs. And bacteria that can chew up on these chemicals are probably being selected to live in these types of tumours.

Chris - What are the implications of this finding then? Do you think that this offers us an avenue to management or therapy? Because is it possible to do something to the bacteria and exploit their presence there to destroy the cancer?

Ravid - I think this is the most exciting thing. The fact that you have bacteria in tumours probably implies that they have a lot of crosstalk with the tumour cells, with the immune cells, and they're probably affecting much of the tumor biology that we see. A good example for it is we found, for example, that tumours of the skin... we looked at patients that responded or did not respond to immunotherapy. And we found that there are specific bacteria that are more prevalent in the responders or the non-responders, suggesting that maybe the bacteria also affect the response of these patients to immunotherapy. And if we learn more about how to modulate the bacteria in the tumours we might find completely novel ways to treat cancer patients.