Immune Profile for Successful Cancer Immunotherapy Discovered

In a new study published online June 25, 2018 in Nature Medicine, UC San Francisco researchers have identified a key biological pathway in human cancer patients that appears to prime the immune system for a successful response to immunotherapy drugs known as checkpoint inhibitors. The findings, including initial observations from human tumor samples, mechanistic studies in mouse models, then confirmation in additional patient samples, could better enable clinicians to predict which patients will naturally benefit from these promising new treatments, and potentially to modify the immune response in other patients to allow more people to benefit from these therapies.

Cancers are often able to evade the immune system by activating the “brakes” built into T cells that normally prevent them from attacking the body’s own tissues. By cutting these brakes, checkpoint inhibitor drugs can “wake up” the immune system to the threat of these cancers and has successfully eliminated malignancies in about 20–40 percent of patients with melanoma and certain other cancer types. In the best cases, awakened T cells continue to patrol the body and prevent the cancer from ever coming back. But in the majority of patients, immunotherapies fail to have their intended effect — even with their brakes removed, T cells stay asleep and the cancer continues to spread.

Matthew “Max” Krummel, PhD, a professor of pathology, member of the UCSF Helen Diller Family Comprehensive Cancer Center, and co-inventor of one of the leading forms of immunotherapy, believes the answer may lie in understanding the broader community of immune cells that occupy the tissue surrounding a tumor, such as the dendritic cells that guide T cells to their targets or the natural killer cells that act as first responders to detect and kill cancer cells before T cells arrive. 

“If you want to stimulate T cells to attack cancer, do you need to recruit any specific allies in the tumor first?” Krummel asked. “We didn’t know who were the good and bad partners within the immune system, so we began systematically taking apart tumors and asking of every cell type that was in it, ‘Can you activate T cells?’”