Until recently, barriers to immunotherapy clinical successes for pancreatic cancer have been due to a lack of understanding of the immune pathways within the pancreatic tumor microenvironment that hinder successful immune responses. Recent advances have identified new targets for developing cancer specific vaccines and new targets for modulating the tumor microenvironment to allow more potent activation and improved access of vaccine induced immune responses. We are just learning that non-neoplastic cells, including cancer-associated myofibroblasts, regulatory T cells, dendritic cells, myeloid-derived suppressor cells, and tumor-associated macrophages, are hijacked by pre-invasive and invasive cancer cells to create a tolerogenic tumor microenvironment. Current research is focused on elucidating the mechanisms of this tolerogenic polarization within the tumor microenvironment with the goal of tipping the balance in favor of an anticancer immune response. With the recent advances in molecular technologies and the development of relevant pancreatic cancer mouse models, it is now within our reach to dissect the inhibitory pathways within the pancreatic tumor microenvironment. This will in turn, lead to new therapeutic opportunities that will eliminate these barriers and convert this deadly cancer into a treatable disease.
1. Keenan et al. A Listeria vaccine and depletion of Tregs activate immunity against early pancreatic intraepithelial neoplasms and prolong the survival of mice. Gastronterology 2014;146:1784-994.
2. Lutz et al. Immunotherapy converts nonimmunogenic pancreatic tumors into foci of immune regulation. Cancer Immunology Research 2014; 2(7):616-31.
3. Kouo et al. Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells. Cancer Immunology Research 2015;3(4):412-23.
[Supported by grants from the National Cancer Institute, National Institutes of Health (P50CA062924, R01CA122081, P30CA006973, and U19CA113341 to E.M.J.), and supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer.]
Citation Format: Elizabeth M. Jaffee. Combinatorial immunotherapies with the potential to reverse the carcinogenesis process [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA26.
- ©2016 American Association for Cancer Research.