Combinatorial Immunotherapy Converts Pancreatic Cancers into an Immunologic Disease Elizabeth M. Jaffee, M.D. The Sidney Kimmel Cancer Center at Johns Hopkins
Barriers to immunotherapy clinical successes for pancreatic cancer have been due to a lack of understanding of the immune pathways within the tumor microenvironment that hinder successful immune responses. We now know 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. 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. We are now developing combinatorial immunotherapies of T cell inducing agents with modulators of T cell down regulatory signals. These studies have shown for the first time that traditionally “non-immunogenic” cancers can be converted into tumors susceptible to immunotherapy. Results from pre-clinical and clinical studies will be discussed. References
Lutz et al. Immunotherapy converts nonimmunogenic pancreatic tumors into foci of immune regulation. CIR 2014; 2(7):616-631.
Le DT, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013; 36 (7): 382-9.
Tsujikawa T, et al. Quantitative Multiplex Immunohistochemistry reveals Myeloid-inflamed Tumor-Immune Complexity Associated with Poor Prognosis. Cell Reports,2017; 19:203-217.
Yarchoan et al. Targeting neoantigens to augment antitumour immunity. Nature Reviews Cancer, 2017.
Credits: None available.
You must be logged in and own this product in order to post comments.