Lung cancer is the leading cause of cancer death in Canada and worldwide, affecting tens of thousands of people each year. While smoking is a major risk factor, many people diagnosed with lung cancer have never smoked.
In recent years, immunotherapy has transformed care for a portion of lung cancer patients by helping the immune system recognize and attack cancer. However, doctors still cannot reliably predict who will benefit, making treatment decisions challenging.
With $525,000 in funding from a Terry Fox New Investigator Award, Dr. Katey Enfield, scientist at the BC Cancer Research Institute, and her team are working to change that. Their research aims to better understand why some patients respond to immunotherapy while others don’t, with the goal of identifying new biomarkers to guide lung cancer treatment.
“There is a global effort to understand why immunotherapy is only effective in some cancer patients,” says Dr. Enfield. “By gaining a better understanding of the biology of treatment response, we hope to improve the toolkit doctors can use to determine which treatments are most likely to work for each patient.”
To date, much research on the immune response to lung cancer has focused on T cells, a type of white blood cell that can directly kill cancer cells. But emerging evidence suggests B cells, another immune cell, may also play an important role.
B cells make antibodies that help the immune system identify threats and flag them for destruction. In earlier work, Dr. Enfield and colleagues discovered that some lung cancer patients produce antibodies against a protein called HERVK, which can become active in cancer cells but is normally switched off in healthy tissue.
Studies have also linked the presence of B cells in lung tumours to stronger immune responses and better outcomes with immunotherapy. However, researchers still don’t understand why only some patients develop these antibody responses or how the tumour environment influences them.
To answer these questions, Dr. Enfield’s team will use cutting-edge technologies to create detailed maps of lung tumours at the single-cell level, revealing how cancer cells and immune cells are organized and interact. By studying tumours from both smokers and people who have never smoked, they hope to identify common patterns that explain why some patients generate stronger antibody responses than others.
The team will also measure antibodies in patients’ blood to see if they can serve as biomarkers for immunotherapy response. If successful, this work could lead to a simple blood test to help predict who is likely to benefit from treatment – and potentially help doctors monitor tumour development or identify patients at higher risk – without invasive procedures.
“Interdisciplinary collaboration is key to making discoveries that improve outcomes for patients,” says Dr. Enfield, who will work closely with mentors and Terry Fox New Frontiers Program Project Grants teams studying immunotherapy and lung cancer.
“Support from the Terry Fox New Investigator Award allows me to launch a research program focused on improving how we predict immunotherapy response in lung cancer,” she adds. “If we can identify better biomarkers, we could help ensure more patients receive treatments that are most likely to benefit them.”