TIL therapy is a live cell treatment where a patient’s tumor is surgically removed and sent to a lab where it is dissected to remove the immune cells that have found and penetrated the tumor. Those immune cells are grown by the millions and then re-infused in the patient to attack their cancer.

For their study, the researchers compared responding and non-responding patients from a clinical trial previously conducted at Moffitt. They found that for non-responding patients, the infused TILs failed to stay active in their bodies over time. Additionally, certain tumor antigens, or molecules that immune cells recognize as threats, disappeared from the cancer cells. This may have allowed the tumors to escape immune detection.

“This research helps us understand why TIL therapy does not work for everyone,” said Chao Wang, Ph.D., a clinical science researcher at Moffitt and co-author of the study. “By identifying these challenges, we can explore new ways to make this treatment more effective. We took a deep dive into every facet we could to unravel the mystery of this process.”

The researchers looked at tumor samples from patients before and after treatment. They discovered that patients who responded well to TIL therapy had T cells that remained in the body longer and continued to fight the cancer. Those who did not respond had T cells that weakened or disappeared quickly.

“Our results suggest that future treatments should focus on improving T-cell survival and targeting stable tumor antigens to give patients a better chance at success,” said Ben Creelan, M.D., a medical oncologist in Moffitt’s Thoracic Oncology Department and co-author of the study. “If we can develop strategies to help T cells last longer and maintain their ability to attack tumors, we may be able to enhance the effectiveness of TIL therapy. This could mean more durable responses and better outcomes for patients with advanced lung cancer.”

These findings could lead to advancements in lung cancer treatments by helping doctors select better T cells for therapy using gene editing and developing ways to reintroduce the missing antigens to prevent tumors from avoiding the immune system.

The researchers also made the sequencing and materials available to other researchers worldwide, through National Institutes of Health archives, to help foster collaboration this field.

Their study was supported by Stand Up To Cancer Foundation (SU2C-AACR-CT04-17), Barbara Bauer Prelude to a Cure Foundation, ER Squibb and Sons, Iovance Biotherapeutics, the National Cancer Institute (P30-CA076292), the Cancer Research Institute and the Troper Wojnicki Foundation.