Published online Jun 10, 2017. doi: 10.5306/wjco.v8.i3.230
Peer-review started: February 14, 2017
First decision: March 7, 2017
Revised: March 18, 2017
Accepted: April 18, 2017
Article in press: April 20, 2017
Published online: June 10, 2017
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses. However, single checkpoint blockade was ineffective in pancreatic cancer, highlighting the challenges including the poor antigenicity, a dense desmoplastic stroma, and a largely immunosuppressive microenvironment. In this review, we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy. These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
Core tip: Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States. Pancreatic cancer is one of nonimmunogenic cancers that lacks of optimal treatments especially from immunotherapy prospective. Therefore, combining immune checkpoint therapies with other treatment modalities in pancreatic cancer will be the best strategy to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.