A team of researchers led by Ludwig Chicago Co-Director Ralph Weichselbaum has published a study suggesting a new approach to improving outcomes of cancer immunotherapy. Their approach combines local radiation therapy and anti-cancer vaccines with checkpoint blockade. They report in the June 13 issue of Oncotarget that this combination of treatments opened up typically unresponsive pancreatic cancer tumors in mice to immune cell infiltration, often inducing immunologic control of tumor growth.
“Our results provide a step-by-step strategy to break the immune barriers that protect aggressive tumors by converting so-called ‘cold,’ or non-T cell inflamed tumors, to a ‘hot,’ or T cell-inflamed phenotype,” said Weichselbaum, who is also the Daniel K. Ludwig Distinguished Service Professor and Chairman of Radiation and Cellular Oncology at the University of Chicago.
Pancreatic tumors tend to be resistant to immunotherapy, displaying low infiltration by CD8+ T cells, which kill cancer cells. Efforts by Weichselbaum and colleagues to boost the immune response with a cancer vaccine had little impact on tumor growth, even when paired with checkpoint blockade. Adding local radiation therapy to the tumor vaccine, however, did enhance T cell infiltration into tumors. Adding a checkpoint blockade after a standard dose of radiation as well as a vaccine tipped the balance, inhibiting tumor growth and extending the survival of tumor-bearing mice. The full version of this news release is available here.