Journal
CLINICAL CANCER RESEARCH
Volume 23, Issue 7, Pages 1656-1669Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-16-2318
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Funding
- Viragh Foundation
- Skip Viragh Pancreatic Cancer Center at Johns Hopkins
- Bloomberg-Kimmel Institute for Cancer Immunotherapy
- NCI SPORE in Gastrointestinal Cancers [P50 CA062924]
- NIH [R01 CA184926, T32 CA009071]
- Stand Up To Cancer - Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant [SU2C-AACR-DT14-14]
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Immunotherapy has changed the standard of care for multiple deadly cancers, including lung, head and neck, gastric, and some colorectal cancers. However, single-agent immunotherapy has had little effect in pancreatic ductal adenocarcinoma (PDAC). Increasing evidence suggests that the PDAC microenvironment is comprised of an intricate network of signals between immune cells, PDAC cells, and stroma, resulting in an immunosuppressive environment resistant to single-agent immunotherapies. In this review, we discuss differences between immunotherapy-sensitive cancers and PDAC, the complex interactions between PDAC stroma and suppressive tumor-infiltrating cells that facilitate PDAC development and progression, the immunologic targets within these complex networks that are druggable, and data supporting combination drug approaches that modulate multiple PDAC signals, which should lead to improved clinical outcomes.
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