A Look at the Immune System When Fighting Lung Cancer

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Topics include: Treatments and Understanding

Dr. David Carbone and Dr. Scott Antonia walk us through the process of angiogenesis inhibitors, which is the process of starving the cancer of its blood supply; essentially stopping the growth progression of the cancer cells. They define for us what a tumor is, how it is fed, and how it sustains itself. The goal with angiogenesis inhibitors is to starve the tumor of its nutrients, so it will die. Proteins are what kill these tumors, and they soak up all the nutrients they need to survive. Along with these treatments, both doctors discuss more treatments, such as immunotherapy, curative surgery and stereotactic body radiation, to consider.

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Okay. Angiogenesis inhibitors you referred to this, Scott, a little bit.  So you’re trying to starve the cancer of its blood supply in a way?

Dr. Antonia:        

Right. All of the mechanisms aren’t all that simple. But that is a good starting way to think about these.  So a tumor is a tissue. It’s a tissue just like any other tissue in your body. It’s made up of cells that need oxygen, and they need glucose. They need sugar to live. And if you stop blood flowing into that, just like any other part of your body, if you stopped its blood flow to that organ, there’s death of that.  And it turns out there are growth factors that are made by tumors that are growth factors for blood vessels. 

And so these treatments are proteins. They’re antibodies. They’re antibodies that can bind to and think of it as soaking up that growth factor, so that growth factor can’t work to allow those blood vessels to grow in. 

Andrew Schorr:                  

Okay. And there are some listings of that.  Okay. Let’s go on. So immunotherapy, so, David, we talked about these cells going haywire. When you developed cancer, has your immune system, if you will, let you down? Has the cancer cell outsmarted your immune system, which would normally be killing abhorrent cells?

Dr. Carbone:       

I think that’s a good way to look at it.  Anytime you have a tumor that you can see, it’s clear that the immune system has not been effective in controlling it.  It may have slowed it down. It may have eliminated other tumors that you didn’t even know you had in the past.  But tumors are quite adaptable. They acquire many mutations that let them grow better.

And one of those abnormalities, and one of the things they do is figure out ways to avoid the immune system. And we’re trying to catch up with that tumor and figure out how they avoided it and then fix that problem. 

Andrew Schorr:                  

Let’s talk about just this concept for a second. Do you remember the idea of the boy in the bubble because he had no immune system? So anything that’s in this room, maybe something floating around, could kill him—virus, bacteria, etc.

So all of our immune systems have been doing a really terrific job that you didn’t get a cold, or you didn’t get some virus or things like that.  Doing a wonderful job. But sometimes, the cancer cell outsmarts it. So, Scott, is it the idea that the cancer cells that developed had this sort of protective shield? They were like invisible or the T cells, the various parts of the immune system were kind of like the blood hound that stayed asleep in the corner and didn’t wake up? 

Dr. Antonia:        

It’s very complicated.  And it turns out there are lots of ways that tumors evade rejection by the immune system.  I told you, there are mutations in genes. Those mutations in a gene, it’s a change in the DNA. The DNA is a template for a protein.  So if the gene has changed, the protein that’s made off of it is changed.  And so our immune systems should think of that tumor as foreign.

Just like if I transplanted a kidney from one person to another, it would be rejected.  It should be. But our immune systems, not only do they have to be turned on to eliminate foreign invaders, they have to be turned off.  So if we get the flu, we need to marshal our immune system.  The cells of our immune system need to be turned on and get rid of that virus. But then a week later, when the virus is gone, we better shut down our immune system, otherwise, we’d just be one big bag of inflammation and get sick and die from that.

So all of our cells of our immune system have a program of, after they’re activated, some period of time later, they start expressing some proteins that shut themselves down. And that’s what happens. And so tumors take advantage of that. So it’s not an abnormal immuno suppression.

It’s just a co-opting or a taking over of a naturally occurring way that we all shut down our own immune systems.  So the drug that was mentioned before, the way that it works is to target the middle of tumors. So there are lots of potential reasons why tumors evade rejection. One is they may not allow enough cells of the immune system to be made. 

The next thing is, even if someone makes enough of those cells, another problem is sometimes, they don’t get into the tumor. And then the third sort of general problem is, when they get into the tumor, they’re shut down.  And that’s what this nivolumab (Opdivo) does and other PD1 drugs.  There are a number of them that are coming…

Andrew Schorr:                  

…what does PD1 stand for, by the way? 

Dr. Antonia:        

PD1 is one of these proteins. It’s an immune checkpoint protein. And it is one of those off switches on the surface of a lymphocyte.

And then tumors take advantage of that. They can express the protein that can flip that off switch. So when those immune cells get into the middle of the tumor, they encounter this protein that flips their off switch, and they’re shut down. What these drugs do, these PD1 blockers, they bind to that off switch so the tumor can’t flip it anymore. 

Andrew Schorr:                  

They lock the switch on.                 

Dr. Antonia:        

They prevent it from being turned off.  So it lets those tumor cells do what they want to do and that is kill the tumor.

Andrew Schorr:                  

Okay. Now, this whole area of immunotherapy, David, is changing.  There are other drugs in trials. We hope there will be others approved before long. So is the idea that they—one idea would be get into the cell and let it to its job.  There are other aspects of immunotherapy, too.  Tell us about those. 

Dr. Carbone:       

Well, one of the most important things about this new class of inhibitors, besides being effective by themselves, they really tell us that immune therapy can work.  There has been a lot of nihilism about that. And 20 years ago, when I wrote my first research grant on immune therapy of lung cancer, it was almost laughed at.  They said lung cancer, immune therapy, that’s ridiculous. It can’t ever work.

But the truth is that there are many mechanisms that tumors use to avoid the immune response, as Scott said.  And we’ve just got one now in patients, that’s ones have been approved. But I’m hopeful that like we’ve found different mutations that can be targeted differently, we will, one by one, understand all the mechanisms that the cancer cell uses to turn off your immune system.  And we’ll be able to have a number of drugs targeting each of those mechanisms and better understand how a given person’s tumor avoids the immune system.

So you can go right after how that tumor switched that switch and turned off the immune system and not just use the same drug in everybody.

Andrew Schorr:                  

Okay. I just want to catch up, make sure everybody is caught up for a second.  We didn’t mean to gloss over surgery. There are different types of surgery. And I know we have things in your packet, and we can talk more about that if you have questions. We have, of course, the medical oncologists who are often the leader of your team, particularly as cancer develops.

And you may have a radiation oncologist, many of you do, too. So we can talk about radiation at some point. But we’ve kind of moved forward into this immunotherapy area, because wouldn’t it be great if your own body could fight the cancer that it, if you will, missed the first time?

Dr. Carbone:       

The fact is that surgery though has dramatically improved over the last few years as well.

Now, we can do curative surgery with patients having three Band-Aids on their chest instead of the foot-long scar that people had years ago. Do it robotically. We have advanced staging techniques that let us biopsy lymph nodes in ways that we couldn’t have done 20 years ago. So like medical therapy, surgery has also improved dramatically in the last decade or two. 

Dr. Antonia:        

As has radiation therapy.  Very similar. We have these techniques called stereotactic body radiations.  So if someone doesn’t have enough lung capacity to live after taking out a piece of the lung with the tumor in it, we can still cure those people with focused radiation, stereotactic radiation and even the people who have the locally advanced disease, the stage III disease. Again, we understand now better doses and schedules and radiation fields that lessen the toxicity and improve the outcomes, the cure rates.

Andrew Schorr:                  

One of you, I think last night, we were talking. And somebody used the phrase we used to treat lung cancer kind of with a blunderbuss or sort of a shotgun where there was a broad surgery, broad radiation, broad medicines. And now, we’re really getting to some people call it precision medicine, right, and personalized medicine.  

So how do you get what’s right for you? And if we said that things are changing, in some areas, we know it’s changing a lot.  There have been some early successes. There’s a sense of this coming broadening more in lung cancer. How do you take advantage of that? We’re going to talk about more of that.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on March 15, 2016