Fri July 5, 2013

Can White Blood Cells Spread Cancer?

Originally published on Fri July 5, 2013 1:55 pm



This is SCIENCE FRIDAY. I'm Ira Flatow. White blood cells are part of our body's defense system. Their job is to attack invaders, and one of the first white blood cells sent out is the neutrophil. These neutrophils put out a trap to capture and destroy the invaders. But here's where it gets interesting, because in a new study, researchers say they have shown that these nets might actually activate and spread the cancer cells. It's the exact opposite of what you want. But there may be a way to counteract this problem.

Joining me now to talk about these findings is Dr. Lorenzo Ferri. He's associate professor of surgery and oncology at McGill University in Montreal, senior author in the study that was published in the journal of clinical investigation. Welcome to the program.

LORENZO FERRI: Oh, thank you very much. My pleasure to be here.

FLATOW: Tell us about this. What was the first clue that the white blood cells might be spreading the cancer?

FERRI: Well, this is sort of a long line of investigation that we and then others around the world have had. It sort of starts out - I'm a surgeon, and so - and I operate on a lot of people with cancer. And, unfortunately, despite our best efforts, in spite of what we do, there's a complication rate associated with cancer surgery between 15 and 20, 25 percent, in which many of these are infections.

So it came out of clinical scenarios where we found that people who had a serious - not all people, but some people have had serious infectious complications after surgery. The cancer - some patients, the cancer would come back earlier than expected, and in a much more aggressive manner than we would expect. And so this made us think maybe there was something going on with some direct interaction between the infection and the cancer itself.

So this led us to the cellular players of the infection, and that really is the neutrophil. And the neutrophil, as you mentioned, is the first white blood cell to be recruited inside an infection. And we've - there's a lot of clinical studies that have shown that people with high neutrophil counts have poor outcomes from surgery, from cancer surgery. And that led us to do some animal studies where, if you got rid of the neutrophils, we actually made - we were able to reduced the cancer significantly. And if we gave the neutrophils back the cancer back in mice.

FLATOW: Wow. Wow. So you think this is an entirely new way...

FERRI: I mean, I think...

FLATOW: ...the cancer spreads.

FERRI: I do. I do, indeed. I mean, I think the - we know that neutrophils - we've been working on neutrophils in particular over the past five to seven years. But the implication of the nets themselves, this web of DNA is an entirely novel approach, or at least newly described approach in order - the way this cancer can spread.

FLATOW: Mm-hmm. So is there a way, then, to get rid of the neutrophils and stop the spread of the cancer?

FERRI: Well, neutrophils are - as you mentioned, they are an integral part of fighting infection. So, I mean, to get rid of them completely is, I think, will do people a disservice. But what we can do is see if we can identify sort of a bit more selective reduction of maybe the certain way that they function, such as these neutrophil extracellular traps.

And that's exactly what our study shows, is that if you can target these webs and still have the neutrophils maintain some of their antimicrobial function and target these webs - which is only one of many ways they can attack bacteria - we may actually impact people in a positive manner.

FLATOW: Are these actually physical webs that the cancer - the neutrophils make? They - like going fishing? They're making a net, sort of thing?

FERRI: Well, I guess similar (unintelligible) one of my residents and students in the lab like to call it, it's more like a Spider-Man web, if you will, which exuded from the neutrophil. Basically, these neutrophils, when they're activated by bacteria and other infections, they can - they basically externalize their DNA, their nuclear DNA and create a - sort of an actual net, if you will. It really is a net, is the appropriate acronym, because it does create a sort of web of very sticky DNA that's decorated with proteins.


FERRI: And so it actually does look - if you look under the microscope, it does actually look like a web.

FLATOW: And so if you can find a way to stop them from making that web, that's what you're looking for.

FERRI: Exactly. But it's really the timing, the timing and exactly the right people in order to do that. I mean, we have, at least in the lab, been able to inhibit these nets from forming, but also break them down once they have formed.

FLATOW: Was it difficult to do that?

FERRI: No. There are actually medications that are currently available right now and being used for other circumstances, non-cancer circumstances. So it's - they're readily available. These - at least one of them is currently used routinely in the treatment of some patients who don't have cancer. And so it's a relatively simple approach, basically, destroying the DNA.

FLATOW: So can you actually try it out? Since it's an approved drug, can you try it out on cancer patients that you're...

FERRI: I think there are a few steps before we can go to that direction. But clearly, it has been shown to be a safe drug. It's used primarily right now - it's approved for cystic fibrosis patients in order to break down sick DNA in their sputum. But it has been given intravenously. And that's where we would need it if we're going to use it in humans. So it is already - we know it's a safe drug, and has a very large safety window. So it's - and a very few side effects.

So it is something that can be used, but, as we mentioned, it's really important to balance the function of neutrophils and their antimicrobial aspect, as well as their cancer. So what we're doing right now is trying to find out exactly when is the right timing and how to - and is it better to go after very specific areas that are on the net, or does he destroy the nets completely?

FLATOW: Because if you go in there too early, you get rid of the white - the good ones, the neutrophil doing the job you want them to do before they set up their nets? Or you want to get them at the right time, so they're still doing the good stuff.

FERRI: Exactly. I mean, you want to make sure they still have enough antimicrobial function so it doesn't make the patient sick. And what we don't want to do is cure the cancer and have someone die of pneumonia. But what we've shown is that it is relatively safe to use in people who don't have cancer, and if we can find just the right time, and whom to use it.

(Unintelligible) use in everyone. It doesn't make sense, but if you can identify patients who are at high risk of infections, or very early on in their infections after surgery, that would seem to be the most appropriate time in general to use this, or to test to see if this has a function in humans.

FLATOW: So what is the next step to get to that point now? Where do you go from here?

FERRI: Yeah, so what we - we're sort of doing a two-pronged approach. First is trying to really find out what is on these nets. I mean, these nets, if you think of them as a Christmas tree that's decorated with those proteins - H protein as an ornament, if you will, that are - and what it does these nets basically create a very high concentration for these proteins to interact with. What it was designed for is bacteria. But we have to find which one of those proteins are actually activating those cancer cells and making them worse. That's one aspect, and we're working on that currently right now.

The next step is really to go into the human level is to really try to find out can - a reliable method in order to measure nets in humans which does not require taking out their livers. That would also be counterproductive for our patients. And then, also, really identify the right timing. So we're working on both of those aspects, both on the clinical level, as well as a - and a basic science level.

FLATOW: Well, good luck to you. Good luck to you, Dr. Ferri for...

FERRI: Thank you very much.

FLATOW: ...for this work, and thanks for taking time to be with us today.

FERRI: It's been my pleasure.

FLATOW: Dr. Lorenzo Ferri, associate professor of surgery and oncology at McGill University. Of course that's in Montreal, Quebec, and he's a senior author on the study that was published in the Journal of Clinical Investigation. Transcript provided by NPR, Copyright NPR.