The pancreatic cancer and immunotherapy experts at Memorial Sloan Kettering Cancer Center (MSK) have shown for the first time why some people with pancreatic cancer live many more years than others with the deadly disease. Pancreatic cancer is one of the most difficult cancers to treat, with just 7 percent of people surviving more than five years after their diagnosis. Less than 2 percent are alive after ten years. This pioneering study found that people with more of the immune cells called T cells present in their tumor survived longer. Researchers were also able to identify the particular components of the tumor that drew in those immune cells. The results, reported in the journal Nature, have implications for the design of more-effective immunotherapy treatments for people with all types of cancer, including the deadly pancreatic cancer. This study lays the groundwork for future research and could potentially lead to the creation of an effective cancer vaccine.
MSK’s Vinod Balachandran, MD, a surgeon-scientist whose laboratory studies pancreatic cancer, and a team of investigators started by asking the simple question: why 5 percent of pancreatic cancer survivors were able to live longer than most of those diagnosed with the deadly disease. They sought to answer this question by examining the differences between tumors from those extremely rare people who survived six years on average and those who did not. Their investigations uncovered that the tumors of long-term survivors of pancreatic cancer had 12 times as many activated T cells, a specialized cancer-fighting immune cell, as people with poorer outcomes. Additionally, researchers discovered that the long-term group’s exceptional survival was linked to the T cells’ ability to recognize novel mutations in cancer proteins that make these cancers resemble infections. The team also discovered that T cells recognizing these novel mutated cancer proteins, called neoantigens, are found in the blood of long-term survivors up to 12 years after the tumors were removed by surgery. This may suggest that these neoantigens could be effective in generating long-lasting “immune memory” against tumors. Based on these striking findings, the group is currently developing clinical trials to examine using these neoantigens as effective cancer vaccines in pancreatic and other cancers.
“These results are exciting, particularly in the field of pancreatic cancer, which can be a very difficult diagnosis and treatment for a patient to contend with,” commented Dr. Balachandran. “For years, research on T cells in pancreatic cancer has been limited as reports suggested that very few of these cells recognized the disease.”
An advantage of this study was its relatively large size. “Before our work, the largest in-depth study looking at long-term survivors of pancreatic cancer had only eight patients,” Dr. Balachandran says. “We had 82.”
Dr. Balachandran also believes that these findings have applications for all cancers, not just pancreatic cancer. “This is a big step forward in discovering why some tumors are more aggressive than others and being able to predict rationally which neoantigens will be the most effective at stimulating an immune response,” he says.
Dr. Balachandran and the team of researchers are working with Genentech and BioNTech to determine how they might use these insights in clinical trials evaluating personalized cancer neoantigen vaccines in a spectrum of cancers, including pancreatic cancer and melanoma.
“Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer” appears in the journal Nature. This study will also be presented by Dr. Balachandran as part of the Presidential Session at the Society for Immunotherapy of Cancer’s annual meeting in 2017.
The corresponding author of this study was Vinod Balachandran, MD, a Memorial Sloan Kettering surgeon-scientist specializing in the treatment of pancreatic cancer and a member of the David M. Rubenstein Center for Pancreatic Cancer Research at MSK.
Co-senior authors on the study were Taha Merghoub, PhD, of the Ludwig Center for Cancer Immunotherapy at MSK, and Steven Leach, MD, former director of the David M. Rubenstein Center for Pancreatic Cancer Research at MSK and now Director of Dartmouth’s Norris Cotton Cancer Center.
Both Dr. Balachandran and Dr. Merghoub are members of the Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering.
This work received financial support from the National Institutes of Health, the Pancreatic Cancer Action Network-AACR Research Acceleration Network supported by Celgene, the Suzanne Cohn Simon Pancreatic Cancer Research Fund, the National Cancer Institute, the Damon Runyon Cancer Research Foundation, Stand Up To Cancer, the V Foundation for Cancer Research, the Lustgarten Foundation, the National Science Foundation, the Parker Institute for Cancer Immunotherapy, Dr. Robert and Mrs. Nancy Magoon, Cycle for Survival, the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, the Ludwig Center for Cancer Immunotherapy, and Swim Across America.