Rahib, L. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913–2921 (2014).
Thomas, R. M. et al. The chemokine receptor CXCR4 is expressed in pancreatic intraepithelial neoplasia. Gut 57, 1555–1560 (2008).
Kim, J. et al. Identification of anti-malarial compounds as novel antagonists to chemokine receptor CXCR4 in pancreatic cancer cells. PLoS ONE 7, e31004 (2012).
Shen, X. et al. Chemokine receptor CXCR4 enhances proliferation in pancreatic cancer cells through AKT and ERK dependent pathways. Pancreas 39, 81–87 (2010).
Lee, S. et al. CCR9-mediated signaling through beta-catenin and identification of a novel CCR9 antagonist. Mol. Oncol. 9, 1599–1611 (2015).
Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).
Cancer Genome Atlas Research Network, Raphael, B. J. et al. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell. 32, 185–203 (2017).
Moffitt, R. A. et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat. Genet. 47, 1168–1178 (2015).
Barretina, J. et al. The cancer cell line encyclopedia enables predictive modeling of anticancer drug sensitivity. Nature 483, 603–607 (2012).
Boj, S. F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324–338 (2015).
Black, M. et al. Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis. Oncotarget 7, 10557–10567 (2016).
Heinrich, E. L., Lee, W., Lu, J., Lowy, A. M. & Kim, J. Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in pancreatic cancer cells. J. Transl. Med. 10, 68 (2012).
Shen, X. et al. CC chemokine receptor 9 enhances proliferation in pancreatic intraepithelial neoplasia and pancreatic cancer cells. J. Gastrointest. Surg. 13, 1955–1962 (2009).
Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448–452 (2003).
Sato, T. & Clevers, H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190–1194 (2013).
Zou, W. & Chen, L. Inhibitory B7-family molecules in the tumour microenvironment. Nat. Rev. Immunol. 8, 467–477 (2008).
Birnbaum, D. J. et al. Prognostic value of PDL1 expression in pancreatic cancer. Oncotarget 7, 71198–71210 (2016).
Johansson, H. et al. Immune checkpoint therapy for pancreatic cancer. World J. Gastroenterol. 22, 9457–9476 (2016).
Tiriac, H. et al. Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy for personalized cancer treatment. Gastrointest. Endosc. 87, 1474–1480 (2018).
Selby, M. J. et al. Preclinical development of ipilimumab and nivolumab combination immunotherapy: mouse tumor models, in vitro functional studies, and cynomolgus macaque toxicology. PLoS ONE 11, e0161779 (2016).
Wang, C. et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol. Res. 2, 846–856 (2014).
Lindemans, C. A. et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528, 560–564 (2015).
Garcia, P. L. et al. Development and histopathological characterization of tumorgraft models of pancreatic ductal adenocarcinoma. PLoS ONE 8, e78183 (2013).
Zeglis, B. M. & Lewis, J. S. The bioconjugation and radiosynthesis of 89Zr-DFO-labeled antibodies. J. Vis. Exp. 96, 52521 (2015).
Nair, A. B. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27–31 (2016).
Shi, C. et al. A drug-specific nanocarrier design for efficient anticancer therapy. Nat. Commun. 6, 7449 (2015).
Barsoum, I. B., Smallwood, C. A., Siemens, D. R. & Graham, C. H. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res. 74, 665–674 (2014).
Huang, L. et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat. Med. 21, 1364–1371 (2015).
Riley, J. L. PD-1 signaling in primary T cells. Immunol. Rev. 229, 114–125 (2009).
Dong, H. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793–800 (2002).
Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012).
Kleffel, S. et al. Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell 162, 1242–1256 (2015).
diMagliano, M. P. & Logsdon, C. D. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology 144, 1220–1229 (2013).
Sebolt-Leopold, J. S. & Herrera, R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat. Rev. Cancer 4, 937–947 (2004).
Moffat, J. G., Rudolph, J. & Bailey, D. Phenotypic screening in cancer drug discovery—past, present and future. Nat. Rev. Drug. Discov. 13, 588–602 (2014).
Brahmer, J. R. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455–2465 (2012).
Royal, R. E. et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J. Immunother. 33, 828–833 (2010).
Weiss, G. J. et al. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer. Br. J. Cancer 117, 33–40 (2017).
Le, D. T. et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J. Immunother. 36, 382–389 (2013).
Patnaik, A. et al. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin. Cancer Res. 21, 4286–4293 (2015).
D’Alincourt Salazar, M. et al. Evaluation of innate and adaptive immunity contributing to the antitumor effects of PD1 blockade in an orthotopic murine model of pancreatic cancer. Oncoimmunology 5, e1160184 (2016).
Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018).
Sunshine, J. & Taube, J. M. PD-1/PD-L1 inhibitors. Curr. Opin. Pharmacol. 23, 32–38 (2015).
Jorgensen, J. T. Companion diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC. Expert Rev. Mol. Diagn. 16, 131–133 (2016).
Robert, C. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372, 320–330 (2015).
Robert, C. et al. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 372, 2521–2532 (2015).
Kerr, K. M. et al. Programmed death-ligand 1 immunohistochemistry in lung cancer: in what state is this art? J. Thorac. Oncol. 10, 985–989 (2015).