A team of researchers at Memorial Sloan Kettering Cancer Center (MSK) and the Ludwig Center at MSK has shown for the first time why some people with pancreatic cancer live many more years than others. The study, authored by Vinod Balanchandran of MSK, Taha Merghoub of Ludwig MSK and Steven Leach of Dartmouth’s Norris Cotton Cancer Center, has implications for the design of more effective immunotherapies for people with all types of cancer and lays the groundwork for research that could lead to novel cancer vaccines.

Pancreatic cancer is extremely resistant to therapy, with just 7% of people surviving more than five years after diagnosis. Less than 2% are alive after ten years. Balanchandran, Leach, Merghoub and their colleagues report in their paper, published in the journal Nature, which patients with relatively large numbers of the immune system’s T cells in their tumors are the ones who survive longer. Long-term survivors of pancreatic cancer may have 12 times as many activated T cells as those with poorer outcomes.

Extended survival, they find, is associated with the ability of T cells to recognize novel mutations in the proteins of cancer cells that make them look foreign to the immune system. The researchers report that T cells that recognize these fragments of mutated cancer proteins, or neoantigens, are found in the blood of long-term survivors up to 12 years after the tumors have been removed by surgery. This suggests that these neoantigens may generate long lasting “immune memory” against cancer cells, and the group hopes to conduct clinical trials examining their use in vaccines for pancreatic and other types of cancer.