The human immune system is an intricate web of checks and balances that usually excels at detecting and destroying foreign invaders, such as bacteria and viruses, while protecting healthy tissue. But sometimes, the checks and balances get confused and stop the immune system from doing what’s right—such as killing tumor cells.
Tumor cells are good at confusing the immune system because they originate from our healthy cells. They can often avoid detection by immune cells. Through several decades of research, we have identified two key protein pathways, PD-L1 and CTLA-4, that lung cancer cells often exploit to stop the immune system from finding and killing them.
By developing treatments called immune checkpoint inhibitors (ICIs) that target these pathways, researchers have been able to unmask tumors, empower the immune system, and create treatment options for patients.
Living Longer Isn’t Enough, Patients Deserve to Live Well Too
These ICI treatments have given people with lung cancer more time to spend with their loved ones. But people don’t just want to live longer, they also want to live better—so they can continue working, enjoying their favorite pastimes, and spending quality time with their family and friends.
There are many types of side effects from immunotherapy, and people are affected to different degrees depending on several factors—overall health, type of cancer, type of medication and the dosage. The most common side effects from lung cancer ICIs are rash, diarrhea, and fatigue. In rarer instances, it can also cause inflammation in the lungs (called pneumonitis) leading to shortness of breath, coughing, and chest pain.
Additional research is needed to understand the causes of these side effects and to develop treatment options that alleviate or eliminate these side effects to provide better quality of life for people with lung cancer.
Driven by Compassion: How a Young Scientist Is Changing Cancer Care
During her medical training, Diane Tseng, MD, PhD, witnessed the profound impact of ICIs on people with lung cancer. “The development and FDA approval of the first immunotherapy in lung cancer left a huge impression on me,” she recalled. “I was so grateful there was new hope for patients with advanced lung cancer.”
But she also saw the reality of these treatments on patients’ lives. “I was also very humbled by the fact that patients were at risk of side effects from immunotherapy. While those side effects were typically mild, occasionally they were severe or even life-threatening.”
My goal is a simple one: find better ways to fight cancer fiercely while treating patients gently.
At the time she was a medical fellow at Stanford University, an influential research paper was published in Science showing that a subpopulation of immune cells (T cells expressing CD8 and KIR proteins on the cell surface) were involved in stopping the immune system from attacking healthy cells.
“When I learned about this study, I was excited. KIR-positive immune cells could be impacting the effectiveness of ICI treatment and they could be playing a role in inflammation-related side effects, such as pneumonitis,” said Dr. Tseng, now assistant professor at the Fred Hutch Cancer Center and University of Washington School of Medicine.
Dr. Tseng and her collaborators, Drs. Joel Neal, Heather Wakelee, and Crystal Mackall, collected blood samples from patients who developed pneumonitis as a side effect of immunotherapy for lung cancer and also from those who didn’t experience pneumonitis. This biobank provides a strong foundation for her research and allows her to ask questions about the underlying causes of pneumonitis.
To delve deeper into the role of this subpopulation of cells, Dr. Tseng received one of the prestigious Career Development Awards from LUNGevity in 2023. Leveraging this award, Dr. Tseng’s research has flourished as she’s explored KIR-positive immune cells to better understand their role in pneumonitis.
“Studying the causes of side effects, like pneumonitis, isn’t just a scientific challenge,” said Dr. Tseng. “It’s a path to a brighter treatment journey for patients and their families.”
Her work offers exciting new avenues to pursue, including the development of a blood test to detect pneumonitis and the deepening of our understanding of the interplay between the immune system and ICI treatment. It also successfully lays the groundwork for a promising career in immune studies.
“Understanding how KIR-positive immune cells behave could unlock new ways to protect patients from side effects and make immunotherapy even more effective,” said Dr. Tseng. “The LUNGevity award didn’t just fund my research—it gave me the foundation to build a program that will impact patients for decades.”