Journal article
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer
VP Balachandran, M Łuksza, JN Zhao, V Makarov, JA Moral, R Remark, B Herbst, G Askan, U Bhanot, Y Senbabaoglu, DK Wells, CIO Cary, O Grbovic-Huezo, M Attiyeh, B Medina, J Zhang, J Loo, J Saglimbeni, M Abu-Akeel, R Zappasodi Show all
Nature | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/nature24462
Abstract
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8 + T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the s..
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Awarded by National Science Foundation
Funding Acknowledgements
We thank A. Rudensky, A. Snyder-Charan, C. Callan, Y. Elhanati, Z. Sethna, J. Leung, J. Ruan, C. Crabtree, P. Garcia, M. Singh, A. McNeil, D. Haviland, J. Melchor and J. Tsoi for discussions, technical and editorial assistance. This work was supported by National Institutes of Health (NIH) R01DK097087-01 Pancreatic Cancer Action Network-AACR Research Acceleration Network Grant (S. D. L.), P30 CA008748-50S4 administrative supplement (S. D. L., V. P. B.), Suzanne Cohn Simon Pancreatic Cancer Research Fund (S. D. L.), National Cancer Institute K12CA184746-01A1 (V. P. B.), Damon Runyon Clinical Investigator Award (V. P. B.), Stand Up to Cancer, Lustgarden Foundation, and the National Science Foundation (J. D. W., B. D. G.), the V Foundation (V. P. B., J. A. M., J. D. W., B. D. G.), the Phil A. Sharp Innovation Award (B. D. G., J. D. W.), Swim Across America, and the Ludwig Institute for Cancer Research (J. D. W., T. M.), and the Parker Institute for Cancer Immunotherapy (D. K. W., C. I. O. C., J. D. W., T. M.). Services by the Integrated Genomics Core were funded by the National Cancer Institute Cancer Center Support Grant (P30 CA08748), Cycle for Survival, and the Marie-Josee and Henry R. Kravis Center for Molecular Oncology.