Pancreatic cancer is one of a number of malignancies that typically lack tumor infiltrating effector lymphocytes and are considered “non-immunogenic” neoplasms. This situation has drastically slowed the development and application of immune-based therapies for these cancers. In this study, we tested the hypothesis that vaccine based immunotherapy can convert pancreatic cancer, a “non-immunogenic” tumor, into an “immunogenic” tumor with infiltrating effector lymphocytes. We recently completed a novel neo-adjuvant and adjuvant study designed to evaluate post-immunotherapy changes within the tumor microenvironment (TME) of primary pancreatic tumors following treatment with the GM-CSF-secreting pancreatic cancer vaccine, given either alone or with immune modulating doses of cyclophosphamide to deplete regulatory T cells. Pathological examination of tumor tissue resected just two weeks following vaccination identified the formation of novel immunotherapy-induced tertiary lymphoid aggregates, organized lymphoid structures that are not observed in tumors resected from unvaccinated patients. This study shows for the first time that treatment with a vaccine-based immunotherapy directly alters the pancreatic cancer TME, allowing infiltration of organized and functional immune structures that convert an immunologically quiescent tumor into an immunologically active tumor. This study also demonstrates that the formation of these immune regulatory structures within the TME is just the first step toward establishing optimal anticancer immune responses within the TME since these lymphoid aggregates can express both effector activating and effector down-regulatory immune signatures. These data support combination immunotherapies that include vaccines that induce T cells and facilitate T cell trafficking into the TME given together with agents that modulate vaccine induced regulatory signals. In addition, these data suggest a new model for developing more effective immunotherapy for traditionally “non-immunogenic” tumors like pancreatic cancer. Finally, the intratumoral signatures identified in this study provide potential targets for developing strategies for modulating the TME and promoting more robust antitumor immune responses in future studies.
Citation Format: Lei Zheng. Vaccines: The igniters of antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA26.
- ©2015 American Association for Cancer Research.