- Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) 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. doi:10.1158/0008-5472.CAN-14-0155
Article CAS PubMed Google Scholar
- Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703. doi:10.1056/NEJMoa1304369
Article Google Scholar
- Thomas AM, Santarsiero LM, Lutz ER et al (2004) Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 200:297–306. doi:10.1084/jem.20031435
Article PubMed Central CAS PubMed Google Scholar
- Winograd R, Byrne KT, Evans RA et al (2015) Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol Res 3:399–411. doi:10.1158/2326-6066.CIR-14-0215
Article CAS PubMed Google Scholar
- Le DT, Lutz E, Uram JN et al (2013) 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. doi:10.1097/CJI.0b013e31829fb7a2
Article PubMed Central CAS PubMed Google Scholar
- Royal RE, Levy C, Turner K et al (2010) Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 33:828–833. doi:10.1097/CJI.0b013e3181eec14c
Article CAS PubMed Google Scholar
- Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT (2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330:827–830. doi:10.1126/science.1195300
Article CAS PubMed Google Scholar
- Laheru D, Jaffee EM (2005) Immunotherapy for pancreatic cancer—science driving clinical progress. Nat Rev Cancer 5:459–467. doi:10.1038/nrc1630
Article CAS PubMed Google Scholar
- Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, Friess H (2012) The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol 9:454–467. doi:10.1038/nrgastro.2012.115
Article CAS PubMed Google Scholar
- Beatty GL, Winograd R, Evans RA et al (2015) Exclusion of T cells from pancreatic carcinomas in mice is regulated by Ly6C(low) F4/80(+) extratumoral macrophages. Gastroenterology 149:201–210. doi:10.1053/j.gastro.2015.04.010
Article CAS PubMed Google Scholar
- Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH (2012) Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21:822–835. doi:10.1016/j.ccr.2012.04.025
Article PubMed Central CAS PubMed Google Scholar
- Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH (2007) Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 67:9518–9527. doi:10.1158/0008-5472.CAN-07-0175
Article CAS PubMed Google Scholar
- Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9:628–638. doi:10.1038/nrm2455
Article CAS PubMed Google Scholar
- Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95:7556–7561
Article PubMed Central CAS PubMed Google Scholar
- Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800. doi:10.1038/nm730
Article CAS PubMed Google Scholar
- Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-gamma. Annu Rev Immunol 15:749–795. doi:10.1146/annurev.immunol.15.1.749
Article CAS PubMed Google Scholar
- Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ (1999) In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia 1:50–62
Article PubMed Central CAS PubMed Google Scholar
- Trevino JG, Summy JM, Gray MJ, Nilsson MB, Lesslie DP, Baker CH, Gallick GE (2005) Expression and activity of SRC regulate interleukin-8 expression in pancreatic adenocarcinoma cells: implications for angiogenesis. Cancer Res 65:7214–7222. doi:10.1158/0008-5472.CAN-04-3858
Article CAS PubMed Google Scholar
- Trevino JG, Verma M, Singh S et al (2013) Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic adenocarcinoma growth irrespective of gemcitabine sensitivity. Mol Cancer Ther 12:2722–2734. doi:10.1158/1535-7163.MCT-12-0719
Article CAS PubMed Google Scholar
- Delitto D, Pham K, Vlada AC et al (2015) Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements. Am J Pathol 185:1297–1303. doi:10.1016/j.ajpath.2015.01.016
Article CAS PubMed Google Scholar
- Bachem MG, Schneider E, Gross H et al (1998) Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology 115:421–432
Article CAS PubMed Google Scholar
- Meng H, Lee Y, Ba Z, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ (2015) In vitro production of IL-6 and IFN-gamma is influenced by dietary variables and predicts upper respiratory tract infection incidence and severity respectively in young adults. Front Immunol 6:94. doi:10.3389/fimmu.2015.00094
Article PubMed Central PubMed Google Scholar
- Li X, Rendon JL, Akhtar S, Choudhry MA (2012) Activation of toll-like receptor 2 prevents suppression of T-cell interferon gamma production by modulating p38/extracellular signal-regulated kinase pathways following alcohol and burn injury. Mol Med 18:982–991. doi:10.2119/molmed.2011.00513
PubMed Central CAS PubMed Google Scholar
- Verhoef CM, Van Roon JA, Vianen ME, Glaudemans CA, Lafeber FP, Bijlsma JW (1999) Lymphocyte stimulation by CD3-CD28 enables detection of low T cell interferon-gamma and interleukin-4 production in rheumatoid arthritis. Scand J Immunol 50:427–432
Article CAS PubMed Google Scholar
- Arumugam T, Ramachandran V, Fournier KF et al (2009) Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res 69:5820–5828. doi:10.1158/0008-5472.CAN-08-2819
Article PubMed Central CAS PubMed Google Scholar
- Trevino JG, Pillai S, Kunigal S, Singh S, Fulp WJ, Centeno BA, Chellappan SP (2012) Nicotine induces inhibitor of differentiation-1 in a Src-dependent pathway promoting metastasis and chemoresistance in pancreatic adenocarcinoma. Neoplasia 14:1102–1114
Article PubMed Central CAS PubMed Google Scholar
- Romagnani P, Annunziato F, Lasagni L et al (2001) Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest 107:53–63. doi:10.1172/JCI9775
Article PubMed Central CAS PubMed Google Scholar
- de Sousa Cavalcante L, Monteiro G (2014) Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 741:8–16. doi:10.1016/j.ejphar.2014.07.041
Article Google Scholar
- Kleeff J, Beckhove P, Esposito I, Herzig S, Huber PE, Lohr JM, Friess H (2007) Pancreatic cancer microenvironment. Int J Cancer 121:699–705. doi:10.1002/ijc.22871
Article CAS PubMed Google Scholar
- Apte MV, Xu Z, Pothula S, Goldstein D, Pirola RC, Wilson JS (2015) Pancreatic cancer: the microenvironment needs attention too! Pancreatology 15:S32–S38. doi:10.1016/j.pan.2015.02.013
Article CAS PubMed Google Scholar
- Neesse A, Algul H, Tuveson DA, Gress TM (2015) Stromal biology and therapy in pancreatic cancer: a changing paradigm. Gut 64:1476–1484. doi:10.1136/gutjnl-2015-309304
Article PubMed Google Scholar
- Lange F, Rateitschak K, Fitzner B, Pohland R, Wolkenhauer O, Jaster R (2011) Studies on mechanisms of interferon-gamma action in pancreatic cancer using a data-driven and model-based approach. Mol Cancer 10:13. doi:10.1186/1476-4598-10-13
Article PubMed Central CAS PubMed Google Scholar
- Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146. doi:10.1038/nature03954
Article CAS PubMed Google Scholar
- Bos R, Sherman LA (2010) CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res 70:8368–8377. doi:10.1158/0008-5472.CAN-10-1322
Article PubMed Central CAS PubMed Google Scholar
- Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF (2004) PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 64:1140–1145
Article CAS PubMed Google Scholar
- Feig C, Jones JO, Kraman M et al (2013) Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA 110:20212–20217. doi:10.1073/pnas.1320318110
Article PubMed Central CAS PubMed Google Scholar
- Hartmann N, Giese NA, Giese T, Poschke I, Offringa R, Werner J, Ryschich E (2014) Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer. Clin Cancer Res 20:3422–3433. doi:10.1158/1078-0432.CCR-13-2972
Article CAS PubMed Google Scholar
- Lakshmi Narendra B, Eshvendar Reddy K, Shantikumar S, Ramakrishna S (2013) Immune system: a double-edged sword in cancer. Inflamm Res 62:823–834. doi:10.1007/s00011-013-0645-9
Article CAS PubMed Google Scholar
- Lunardi S, Jamieson NB, Lim SY et al (2014) IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival. Oncotarget 5:11064–11080
Article PubMed Central PubMed Google Scholar
- Chaturvedi P, Gilkes DM, Wong CC et al (2013) Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest 123:189–205. doi:10.1172/JCI64993
PubMed Central CAS PubMed Google Scholar
- Zipin-Roitman A, Meshel T, Sagi-Assif O, Shalmon B, Avivi C, Pfeffer RM, Witz IP, Ben-Baruch A (2007) CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. Cancer Res 67:3396–3405. doi:10.1158/0008-5472.CAN-06-3087
Article CAS PubMed Google Scholar
- Walser TC, Rifat S, Ma X et al (2006) Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res 66:7701–7707. doi:10.1158/0008-5472.CAN-06-0709
Article CAS PubMed Google Scholar
- Kawada K, Sonoshita M, Sakashita H et al (2004) Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res 64:4010–4017. doi:10.1158/0008-5472.CAN-03-1757
Article CAS PubMed Google Scholar
- Schober M, Jesenofsky R, Faissner R, Weidenauer C, Hagmann W, Michl P, Heuchel RL, Haas SL, Lohr JM (2014) Desmoplasia and chemoresistance in pancreatic cancer. Cancers (Basel) 6:2137–2154. doi:10.3390/cancers6042137
Article CAS Google Scholar
- Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE (2007) Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 14:3629–3637. doi:10.1245/s10434-007-9583-5
Article PubMed Google Scholar