With each issue, Trib+Health brings you an interview with experts on issues related to health care. Here is this week’s subject:
Dr. Tyler Curiel is a professor in the Department of Medicine and Department of Microbiology, Immunology and Molecular Genetics at the Joe R. & Teresa Lozano Long School of Medicine at the University of Texas Health Science Center at San Antonio. His areas of research focus on cancer immunotherapy and aging, among other things, and he was recently awarded a grant by the National Institute of Health to continue his cancer research.
Editor’s note: This interview has been edited for length and clarity.
Trib+Health: Can you expand on your recent findings in cancer immunology?
Tyler Curiel: After around 40 years of hard work from our group and other groups' parts, we’re seeing some real successes with immunotherapy for cancer. The big breakthrough came in understanding what the barriers were and overcoming those. One area where we have seen a rapid expansion of knowledge is in immune checkpoint blockade.
When you have a cancer or any type of insult on your body, it turns your immune system off. Cancers have figured out various off switches, and they give a signal to your immune response that the mission has been accomplished. We showed that you can make antibodies to block immune checkpoints — your immune system has an off switch out there, and if we can prevent the off switch from doing what it's supposed to do, it can kill the cancer.
For the first time ever, we are starting to see patients with advanced-stage cancers responding to this checkpoint blockade kind of therapy.
Trib+Health: What are some problems you've encountered in the field?
Curiel: Although there’s been really good success with this immune checkpoint strategy, the truth is that it only helps a minority of patients. The problem is most people don’t respond, and the other thing is we are not good at predicting who will and won’t respond.
The question is, how do these immune checkpoints work, and what are they really doing? If they work the way we think they will, then they should be working better, and we should be able to better predict who will and won’t respond.
We have now shown that these immune checkpoint molecules have a lot of extra functions nobody knew about. There are inner signals inside tumor cells that give the cell additional instructions, including things like, "grow faster," "resist therapy," "spread to different parts of the body," and "attract cells to help turn the immune response off," among other things.
Now that we know this, it helps our understanding of who can and can't respond to therapy. We've conducted clinical trials with mice to help overcome new barriers and make this work better.
Trib+Health: What does your work in cancer immunotherapy look like now?
Curiel: We're now talking to biotech and pharma companies to develop new strategies for clinical trials so we can go out there and ask if what we found with mice will work with humans, too. Can we help explain why some people respond really well, but most not at all? We've done all of this in our mice.
Now we have to ask if we can do this in humans, and it looks like we can. That's what another big award from the National Cancer Institute is designed to do, and we are guardedly optimistic this will work.
Trib+Health: What are additional advancements you've made in the aging field, another area of your research?
Curiel: Most people probably don't recognize that the No. 1 risk factor for cancer is age — it's not smoking or what you eat. It's no secret the U.S. and world are aging, and there's going to be a big uptick in cancer, just based on that fact.
Many colleagues have shown that immunotherapies that work really well in young people fail in old people. That's not a surprise, but the big surprise is we've been looking at the immune system, and when your immune system ages, the thought was everything works the way it used to work, it just doesn't work as well.
It turns out, that's not true. Some cells that didn't used to be there when you were young start appearing when you're old, and they do weird things we never knew about. And cells that were there when you were young, instead of doing less of what they used to do, do more of something that's bad for you.
Based on this, we developed the first therapy that's ever been described that will be effective as immunotherapy for cancer in aged mice but not young mice. We are able to understand what happens to the immune system when you age, and we developed therapies that are specific toward aged immune systems so that they will work when you are old and most at risk for cancer.
Trib+Health: Tell me about your presidential award you received in March.
Curiel: The presidential award is to recognize a lot of work from my lab over the last 10 years here at the Health Science Center that helped bring us to this particular point, but also other areas we are working on to improve cancer immunotherapy.