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Gastroenterology. 2019 Jan 17. pii: S0016-5085(19)30054-X. doi: 10.1053/j.gastro.2018.12.038. [Epub ahead of print]

Broadening the impact of immunotherapy to pancreatic cancer: Challenges and opportunities.

Author information

1
Department of Surgery, David M. Rubenstein Center for Pancreatic Cancer Research, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: balachav@mskcc.org.
2
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: gregory.beatty@uphs.upenn.edu.
3
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address: stephanie_dougan@dfci.harvard.edu.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer in the US by 2025 1, with 5-year survival at less than 10% 2. In other recalcitrant cancers, immunotherapy has shown unprecedented response rates, including durable remissions after drug discontinuation. However, responses to immunotherapy in PDAC are rare. Accumulating evidence in mice and humans suggests that this remarkable resistance is linked to the complex, dueling role of the immune system in simultaneously promoting and restraining PDAC. In this review, we highlight the rationale that supports pursuing immunotherapy in PDAC, outline the key barriers that limit immunotherapy efficacy, and summarize the primary preclinical and clinical efforts to sensitize PDAC to immunotherapy.

KEYWORDS:

PDAC; clinical trials; immunity; immunotherapy; pancreatic cancer

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