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.
Keywords: Adoptive transfer, cancer vaccine, immune checkpoints, immunosuppression, immunotherapy, immune tolerance,
pancreatic adenocarcinoma, tumor microenvironment.
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