Abstract
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer in the United States by 2025, with 5-year survival at less than 10%. 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:
Clinical Trials; Immunity; Immunotherapy; PDAC; Pancreatic Cancer.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents, Immunological / adverse effects
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Antineoplastic Agents, Immunological / therapeutic use*
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Cancer Vaccines / adverse effects
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Cancer Vaccines / therapeutic use*
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Carcinoma, Pancreatic Ductal / immunology
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Carcinoma, Pancreatic Ductal / mortality
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Carcinoma, Pancreatic Ductal / pathology
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Carcinoma, Pancreatic Ductal / therapy*
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Drug Resistance, Neoplasm
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Humans
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Immunotherapy / adverse effects
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Immunotherapy / methods*
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Immunotherapy / mortality
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Lymphocytes, Tumor-Infiltrating / drug effects
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Lymphocytes, Tumor-Infiltrating / immunology
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Pancreatic Neoplasms / immunology
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Pancreatic Neoplasms / mortality
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / therapy*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Treatment Outcome
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Tumor Escape
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Tumor Microenvironment
Substances
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Antineoplastic Agents, Immunological
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Cancer Vaccines