New research is shedding light on reasons cancer immunotherapy can fail, which could lead to more life-saving treatments for patients. Since oncologists began administering immunotherapies to cancer patients, the revolutionary treatments have become a new pillar of care and have saved countless lives. “The T-cells in the body’s immune system are powerful weapons in the battle against cancer, and can be energized to better detect and kill cancer cells with immunotherapy drugs,” says Zihai Li, MD, PhD, the founding director of the Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). Li shares all the details of his groundbreaking immunotherapy research on our Cancer-Free World Podcast. Watch on the video player above or YouTube, and listen on Spotify and Apple Podcasts. Along with the progress, though, immunotherapy has presented some challenges to doctors and researchers, especially when it comes to “chronic cancers,” in which the body constantly engages T-cells. In a recent, groundbreaking study, Li and his colleagues discovered that, in these cases, that constant effort can reduce the functionality of T-cells, which in turn can limit the body’s ability to kill cancer cells — a concept known as T-cell exhaustion. “If a marathoner runs continuously for two hours, they’ll be o.k., but running for 20 hours would be a problem — this is the concept of exhaustion,” Li says. “T-cells try to run that race for a long time without any kind of rest or recalibration, and eventually they can become dysfunctional.” Learn more: Immunotherapy is changing cancer care at Ohio State and beyond. In its landmark study, Li’s team isolated both exhausted and effective T-cells and compared them. Eventually, the team discovered increases in proteins — sometimes referred to as stress proteins — in exhausted T-cells from cancer patients. Further research showed that those stress proteins also tended to solidify in T-cells that lost function. “These stress cells were becoming solid, which we had never seen before,” Li says. “This was an important discovery — something fundamental.” This major step forward in the understanding of immunotherapy could pave the way for improved treatments for patients with several types of cancer. “We want to give the T-cells more weapons to help rejuvenate them so they can win the fight against cancer,” he says. “We have to pay attention to protein quality control.” Li believes immuno-oncology is a foundational piece of the future of cancer care, and that understanding and treating T-cell exhaustion will be a vital part of maximizing the effectiveness of immunotherapy treatments. “I am absolutely optimistic that a vast majority of cancers will be dealt with by immunotherapy,” he says. “This is the most important way forward in treating cancer.” Learn more: Ohio State oncology innovation is saving lives today while helping to build the future of cancer care.