Leveraging lessons from cancer immunotherapy to develop better treatments for autoimmunity

Immunotherapy has transformed cancer treatment, helping countless patients live longer, healthier lives. But researchers are continuing to work to develop a deeper understanding of this game-changing treatment.

In some cancer patients, immunotherapy can unleash the brakes on a harmful response from the immune system, causing what’s called immune-related adverse events, or irAEs for short. In other words, side effects. With more patients undergoing immunotherapy, there’s a pressing need to better understand and manage these immune-driven side effects.

Kristen Pauken, Ph.D., is an MD Anderson scientist working to better understand the immune system and what causes these side effects. The Immunology assistant professor hopes that by studying autoimmune diseases, she’ll be able to uncover insights that unlock successful treatments for both cancer treatment side effects and autoimmune disease.

For Pauken, the research is personal. She herself struggles with Rheumatoid arthritis, an autoimmune disease in which the body attacks the joints. She first started experiencing symptoms during her postdoctoral training.

“I want to be part of the solution to the autoimmunity problem. I want to bring my unique training history in autoimmunity, chronic infection, and cancer to bring more cures to more patients,” she says. “As an immunologist, I believe that if we knew the right buttons to push and levers to pull, we could restore health and homeostasis, not only in cancer, but in autoimmunity as well.”

A path to the lab

Growing up, Pauken could be found in the backyard, playing in the water and conducting science experiments. “I always knew I wanted to be a biologist,” she says. 

As an undergraduate majoring in microbiology at Colorado State University, Pauken wanted to pursue a career in human health. Here, she was introduced to the immune system; she became completely enthralled by how the immune system deals with chronic disease.

After studying chronic parasitic infection for two years, she transitioned to a Ph.D. in immunology at the University of Minnesota. She wanted to learn more about how T cells were regulated in chronic diseases and ended up joining an autoimmunity lab.

“The immune system has developed dozens of ways to protect self-tissues from accidental damage by the immune system, so when it happens, it looks very different from what anti-pathogen or anti-cancer immune responses look like.”

After completing her Ph.D. in autoimmunity, Pauken diversified her immunology expertise, switching gears to study how checkpoint inhibitors could be used to better leverage the immune system in chronic infection and cancer. She completed postdoctoral training in chronic infection at the University of Pennsylvania and then in cancer at Harvard Medical School. In each position, Pauken focused on how delivering PD-1 checkpoint inhibitors impacted the ensuing immune response and host outcomes, focusing on how different the outcomes could be depending on the underlying immune status in the host.

“It was exciting to feel like I was bringing hope to patients. I was identifying barriers to success and coming up with solutions to solve them,” she says.

An unexpected Rheumatoid arthritis diagnosis

Along the way, she started to experience her own issues with an autoimmune disease, and during her postdoctoral training, she received an unexpected diagnosis.

“One day, I started feeling like I was walking on marbles. Within a few weeks, I couldn’t bend any of my fingers because my joints were so swollen,” she says.

Follow-up analyses confirmed that Pauken had developed Rheumatoid arthritis. Like other autoimmune diseases, this disease requires lifelong symptom management through immunomodulatory drugs.

“Hearing those words – ‘We have found that your immune system is attacking your body, and there are no cures, so we need to discuss your symptom management plan’ – still feels surreal,” she says. “Knowing there is no existing clinical solution to your problem is devastating.”

With this diagnosis, Pauken decided to change her research trajectory.

Unlocking the secrets of the immune system

Upon launching her independent research program, Pauken decided there was no better place for her lab than MD Anderson. 

“The pipeline from my bench to patients felt so much shorter at MD Anderson than anywhere else,” Pauken says.

Now, Pauken’s lab is dedicated to finding ways to help those who suffer from immune-driven pathologies, whether those symptoms are caused by immunotherapy drugs or arise spontaneously for reasons that are not well-understood. An estimated 5% to 8% of people in the United States have an autoimmune disease, and once diagnosed, they will have that disease for the rest of their lives. Physicians can help patients manage their symptoms but cannot cure the underlying disease.

At MD Anderson, Pauken has found a collaborative community dedicated to not only curing cancer but also treating and eliminating the side effects. She became an active part of the Immuno-Oncology Toxicity (IOTOX) Leaders Group, which combines the expertise of MD Anderson’s Internal Medicine and Cancer Medicine teams to support clinical, research and education efforts aimed at solving the problem of irAEs and improving the lives of cancer patients.

“Academia can be competitive, but to really make a difference in a space as complicated as irAEs in cancer, it takes a collaborative environment where people with complementary strengths unite for a common cause,” Pauken says. “This is an area where MD Anderson really excels to improve patient care.”

In 2023, she was awarded an Andrew Sabin Family Fellowship to pursue research in skin irAEs. The Sabin Fellowship is a grant given to early-career faculty that frees them to pursue novel or high-risk, high-reward scientific endeavors early in their careers when federal and private funding opportunities often are limited.

Her lab continues to focus on unlocking secrets and shedding light on the immune system, in hopes of easing the burden for all patients.

Pauken stresses that unleashing the brakes with checkpoint immunotherapy has had such a positive impact on the lives of cancer patients. “To continue maximizing the therapeutic impact of checkpoint inhibitors, we must get better at selectively putting the brakes back on pathogenic immune reactions. This is not exclusively a cancer immunotherapy problem: What we learn here has the potential to transform the way we treat autoimmunity, a class of chronic diseases that, despite decades of research, has no cure,” she says. “I wake up every day to the clinical reality of living with a disease with no cure. Being in the research space for autoimmunity gives me hope. It makes me feel like I am contributing to the solution, even though the problem is hard.”

Learn about research careers at MD Anderson.