Immunotherapeutic Approaches in Pancreatic Adenocarcinoma: Current Status and Future Perspectives

Pancreatic adenocarcinoma is highly lethal, and until prevention of this disease is possible, various treatments including the recently developed immunotherapy to improve patients' survival and quality of life are desperately needed. The objectives of this article are to examine the role of tumor-associated immunosuppression in pancreatic cancer development, dissect the cellular and molecular basis of the immunotherapeutic approaches, and discuss the current status and emerging strategies of immunotherapy in this malignant disease. Animal models and experimental evidence have shown that pancreatic tumor-associated stroma produces an immunosuppressive microenvironment, which promotes development and progression of pancreatic tumor. This results from dynamic interactions among pancreatic cancer cells and the immune effector cells through the actions of multiple cytokines and binding of immunomodulatory molecules. Various immunotherapeutic approaches have been developed in attempt to stimulate immune response by cytokine- or tumor-associated antigen-based vaccines, adoptive transfer of immunotoxins or antigen-primed immune cells, or antibodies directed against immune regulators. Results of these clinical studies show that these treatments are generally well tolerated without major serious complications, and demonstrate potential efficacy of immune-based therapies in pancreatic cancer. Strategies to improve the efficacy of immunotherapy may be accomplished by combining it with the conventionally used chemotherapy or targeted agents. Combinatorial approach using molecular profiling and bioinformatics may help identify predictive biomarkers of treatment response as well as identifying potential targets for personalized cancer vaccines. Hopefully, this article will stimulate further research interests and collaborative efforts to optimize therapy for patients with this devastating disease.