title: Strategies for Increasing Pancreatic Tumor Immunogenicity.
abstract: 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.Clin Cancer Res; 23(7); 1656-69. ©2017 AACRSee all articles in thisCCR Focussection, "Pancreatic Cancer: Challenge and Inspiration."
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Burles A
authors.initials: BA
authors.lastname: Johnson
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Yarchoan
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lee
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Laheru
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland. ejaffee@jhmi.edu.|Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D058954:Pancreatic Stellate Cells / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*