In addition, researchers have found that combin- ing immunotherapies with other treatments may provoke an even better clinical response in patients than either treatment alone. Ralph Weichselbaum, MD, Daniel K. Ludwig Distin- guished Service Professor of Radiation and Cellular Oncology, discovered that radiation therapy can improve the efficacy of immunotherapies. Radiation helps activate CD8+ T cells in tumors, while a checkpoint inhibitor helps protect those T cells from immune suppression. In one study, Weichselbaum added a vaccine to the mix and found that the combination of the three therapies helped overcome the non-T-cell-inflamed tumor microenvironment in pancreatic cancer.4 “Our results provide a step-by-step strategy to break the immune barriers that protect aggres- sive tumors by converting so-called ‘cold,’ or non-T-cell-inflamed, tumors to a ‘hot,’ or T-cell- inflamed, phenotype,” said Weichselbaum. A phase I clinical trial led by Jason Luke, MD, assis- tant professor of medicine, and including Steven Chmura, MD, PhD, associate professor of radiation and cellular oncology, combines the PD-1 inhibitor pembrolizumab with stereotactic body radiother- apy (SBRT) in patients with advanced solid tumors. SBRT is a type of radiation therapy that delivers precise doses of radiation to tumors in the body while limiting damage to normal tissue.5 SBRT will also be combined with immunotherapy in upcoming clinical trials for liver cancer, led by Manish Sharma, MD, assistant professor of medicine. Other researchers leading immunotherapy clinical trials include: • Hongtao Liu, MD, PhD, assistant professor of medicine, in hematologic malignancies • Tanguy Seiwert, MD, assistant professor of medicine, in head and neck cancer • Hedy Kindler, MD, professor of medicine, in mesothelioma • Daniel Catenacci, MD, assistant professor of medicine, in gastroesophageal cancer • Jyoti Patel, MD, professor of medicine, in non-small cell lung cancer • Peter O’Donnell, MD, assistant professor of medicine, in bladder cancer • Everett Vokes, MD, John E. Ultmann Professor of Medicine and Radiation Oncology, in non-small cell lung cancer MAKING “COLD” TUMORS “HOT” Another protein that plays an important role in innate immunity—the body’s natural ability to Researchers have found that combining immunotherapies with other treatments may provoke an even better clinical response in patients than either treatment alone. CANCER.UCHICAGO.EDU 3