Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/− pancreatic ductal adenocarcinoma

References

• Ansari D, Gustafsson A, Anderson R. Update on the management of pancreatic cancer: surgery is not enough. World J Gastroenterol 2015; 21:3157-65; PMID:25805920; http://dx.doi.org/10.3748/wjg.v21.i11.3157
   PubMed Web of Science ®Google Scholar
• Fesinmeyer MD, Austin MA, Li CI, De Roos AJ, Bowen DJ. Differences in survival by histologic type of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2005; 14:1766-73; PMID:16030115; http://dx.doi.org/10.1158/1055-9965.EPI-05-0120
   PubMed Web of Science ®Google Scholar
• American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016
   Google Scholar
• Niccolai E, Prisco D, D'Elios MM, Amedei A. What is recent in pancreatic cancer immunotherapy? Biomed Res Int 2013; 2013:492372; PMID:23509731; http://dx.doi.org/10.1155/2013/492372
   PubMed Web of Science ®Google Scholar
• Lepisto AJ, Moser AJ, Zeh H, Lee K, Bartlett D, McKolanis JR, Geller BA, Schmotzer A, Potter DP, Whiteside T. A phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors. Cancer Ther 2008; 6:955-64; PMID:19129927
   PubMedGoogle Scholar
• Morse MA, Nair SK, Boczkowski D, Tyler D, Hurwitz HI, Proia A, Clay TM, Schlom J, Gilboa E, Lyerly HK. The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer. Int J Gastrointest Cancer 2002; 32:1-6; PMID:12630764; http://dx.doi.org/10.1385/IJGC:32:1:1
   PubMedGoogle Scholar
• Kalady MF, Onaitis MW, Emani S, Abdul-Wahab Z, Pruitt SK, Tyler DS. Dendritic cells pulsed with pancreatic cancer total tumor RNA generate specific antipancreatic cancer T cells. J Gastrointest Surg 2004; 8:175-81; PMID:15036193; http://dx.doi.org/10.1016/j.gassur.2003.11.003
   PubMed Web of Science ®Google Scholar
• Akiyama Y, Maruyama K, Nara N, Hojo T, Cheng JY, Mori T, Wiltrout RH, Yamaguchi K. Antitumor effects induced by dendritic cell-based immunotherapy against established pancreatic cancer in hamsters. Cancer Lett 2002; 84:37-47; PMID:12104046; http://dx.doi.org/10.1016/S0304-3835(02)00189-1
   Web of Science ®Google Scholar
• Le DT, Lutz E, Uram JN, Sugar EA, Onners B, Solt S, Zheng L, Diaz LA Jr, Donehower RC, Jaffee EM 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 2013; 36:382-9; PMID:23924790; http://dx.doi.org/10.1097/CJI.0b013e31829fb7a2
   PubMed Web of Science ®Google Scholar
• Kammertoens T, Schuler T, Blankenstein T. Immunotherapy: target the stroma to hit the tumor. Trends Mol Med 2005; 11:225-31; PMID:15882610; http://dx.doi.org/10.1016/j.molmed.2005.03.002
   PubMed Web of Science ®Google Scholar
• Halpert MM, Konduri V, Liang D, Chen Y, Wing JB, Paust S, Levitt JM, Decker WK. Dendritic cell secreted CTLA-4 regulates the T-cell response by downmodulating bystander surface B7. Stem Cells Dev 2016; 15:774-87; PMID:26979751; http://dx.doi.org/10.1089/scd.2016.0009
   PubMed Web of Science ®Google Scholar
• Cheng W, Ren X, Zhang C, Cai J, Liu Y, Han S, Wu A. Bioinformatic profiling identifies an immune-related risk signature for glioblastoma. Neurology 2016; 86:2226-34; PMID:27225222; http://dx.doi.org/10.1212/WNL.0000000000002770
   PubMed Web of Science ®Google Scholar
• Liang D, Halpert MM, Konduri V, Decker WK. Stepping out of the cytosol: AIMp1/p43 potentiates the link between innate and adaptive immunity. Int Rev Immunol 2015; 34:367-81; PMID:26325028; http://dx.doi.org/10.3109/08830185.2015.1077829
   PubMed Web of Science ®Google Scholar
• Hong HJ, Kim E, Jung MY, Kim S, Kim TS. AIMP1 deficiency enhances airway hyperreactivity in mice via increased TH2 immune responses. Clin Immunol 2012; 143:256-65; PMID:22472603; http://dx.doi.org/10.1016/j.clim.2012.02.004
   PubMed Web of Science ®Google Scholar
• Kim E, Kim SH, Kim S, Cho D, Kim TS. AIMP1/p43 protein induces the maturation of bone marrow-derived dendritic cells with T helper type 1-polarizing ability. J Immunol 2008; 180:2894-902; PMID:18292511; http://dx.doi.org/10.4049/jimmunol.180.5.2894
   PubMed Web of Science ®Google Scholar
• Decker WK, Xing D, Li S, Robinson SN, Yang H, Steiner D, Komanduri KV, Shpall EJ. Th-1 polarization is regulated by dendritic cell comparison of MHC class I and class II antigens. Blood 2009; 113:4213-23; PMID:19171878; http://dx.doi.org/10.1182/blood-2008-10-185470
   PubMed Web of Science ®Google Scholar
• Decker WK, Xing D, Li S, Robinson SN, Yang H, Yao X, Segall H, McMannis JD, Komanduri KV, Champlin RE et al. Double loading of dendritic cell MHC class I and class II with an AML antigen repertoire enhances correlates of T-cell immunity in vitro via amplification of T-cell help. Vaccine 2006; 24:3203-16; PMID:16480795; http://dx.doi.org/10.1016/j.vaccine.2006.01.029
   PubMed Web of Science ®Google Scholar
• Halpert MM, Carstens JL, Schissler P et al. Homologous antigenic loading of dendritic cell MHC class I and II initiates AIMp1-mediated TH1 immunity. Submitted.
   Google Scholar
• Jalah R, Rosati M, Ganneru B, Pilkington GR, Valentin A, Kulkarni V, Bergamaschi C, Chowdhury B, Zhang GM, Beach RK et al. The p40 subunit of interleukin (IL)-12 promotes stabilization and export of the p35 subunit. J Biol Chem 2013; 288:6763-76; PMID:23297419; http://dx.doi.org/10.1074/jbc.M112.436675
   PubMed Web of Science ®Google Scholar
• Ruiz AL, Soudja SM, Deceneux C, Lauvau G, Marie JC. NK1.1+CD8+ T cells escape TGF-β control and contribute to early microbial pathogen response. Nat Commun 2014; 5:5150; PMID:25284210; http://dx.doi.org/10.1038/ncomms6150
   PubMed Web of Science ®Google Scholar
• Krupnick AS, Lin X, Li W, Higashikubo R, Zinselmeyer BH, Hartzler H, Toth K, Ritter JH, Berezin MY, Wang ST et al. Central memory CD8+ T lymphocytes mediate lung allograft acceptance. J Clin Invest 2014; 124:1130-43; PMID:24569377; http://dx.doi.org/10.1172/JCI71359
   PubMed Web of Science ®Google Scholar
• Zou Q, Wu B, Xue J, Fan X, Feng C, Geng S, Wang M, Wang B. CD8+ Treg cells suppress CD8+ T cell-responses by IL-10 dependent mechanism during H5N1 influenza virus infection. Eur J Immunol 2014; 44:103-14; PMID:24114149; http://dx.doi.org/10.1002/eji.201343583
   PubMed Web of Science ®Google Scholar
• Dauer M, Herten J, Bauer C, Renner F, Schad K, Schnurr M, Endres S, Eigler A. Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated cytotoxicity induced by tumor lysate-pulsed dendritic cells. J Immunother 2005; 28:332-42; PMID:16000951; http://dx.doi.org/10.1097/01.cji.0000164038.41104.f5
   PubMed Web of Science ®Google Scholar
• Kim HS, Choo YS, Koo T, Bang S, Oh TY, Wen J, Song SY. Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in murine pancreatic cancer. Immunol Lett 2006; 103:142-8; PMID:16313973; http://dx.doi.org/10.1016/j.imlet.2005.10.021
   PubMed Web of Science ®Google Scholar
• Schmidt T, Ziske C, Marten A, Endres S, Tiemann K, Schmitz V, Gorschlüter M, Schneider C, Sauerbruch T, Schmidt-Wolf IG. Intratumoral immunization with tumor RNA-pulsed dendritic cells confers antitumor immunity in a C57BL/6 pancreatic murine tumor model. Cancer Res 2003; 63:8962-8967; PMID:14695214
   PubMed Web of Science ®Google Scholar
• Nair SK, Hull S, Coleman D, Gilboa E, Lyerly HK, Morse MA. Induction of carcinoembryonic antigen (CEA)-specific cytotoxic T-lymphocyte responses in vitro using autologous dendritic cells loaded with CEA peptide or CEA RNA in patients with metastatic malignancies expressing CEA. Int J Cancer 1999; 82:121-124; PMID:10360830; http://dx.doi.org/10.1002/(SICI)1097-0215(19990702)82:1%3c121::AID-IJC20%3e3.0.CO;2-X
   PubMed Web of Science ®Google Scholar
• Mule JJ. Dendritic cell-based vaccines for pancreatic cancer and melanoma. Ann NY Acad Sci 2009; 1174:33-40; PMID:19769734; http://dx.doi.org/10.1111/j.1749-6632.2009.04936.x
   PubMed Web of Science ®Google Scholar
• Mosolits S, Ullenhag G, Mellstedt H. Therapeutic vaccination in patients with gastrointestinal malignancies. A review of immunological and clinical results. Ann Oncol 2005; 16:847-62; PMID:15829493; http://dx.doi.org/10.1093/annonc/mdi192
   PubMed Web of Science ®Google Scholar
• Broomfield S, Currie A, van der Most RG, Brown M, van Bruggen I, Robinson BW, Lake RA. Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy. Cancer Res 2005; 65:7580-4; PMID:16140921
   PubMed Web of Science ®Google Scholar
• Correale P, Cusi MG, Tsang KY, Del Vecchio MT, Marsili S, Placa ML, Intrivici C, Aquino A, Micheli L, Nencini C et al. Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients. J Clin Oncol 2005; 23:8950-8; PMID:16061910; http://dx.doi.org/10.1200/JCO.2005.12.147
   PubMed Web of Science ®Google Scholar
• Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 2005; 11:6713-21; PMID:16166452; http://dx.doi.org/10.1158/1078-0432.CCR-05-0883
   PubMed Web of Science ®Google Scholar
• Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007; 179:977-83; PMID:17617589; http://dx.doi.org/10.4049/jimmunol.179.2.977
   PubMed Web of Science ®Google Scholar
• Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol 2009; 9:900-9; PMID:19336265; http://dx.doi.org/10.1016/j.intimp.2009.03.015
   PubMed Web of Science ®Google Scholar
• Soeda A, Morita-Hoshi Y, Makiyama H, Morizane C, Ueno H, Ikeda M, Okusaka T, Yamagata S, Takahashi N, Hyodo I et al. Regular dose of gemcitabine induces an increase in CD14+ monocytes and CD11c+ dendritic cells in patients with advanced pancreatic cancer. Jpn J Clin Oncol 2009; 39:797-806; PMID:19797418; http://dx.doi.org/10.1093/jjco/hyp112
   PubMed Web of Science ®Google Scholar
• Bauer C, Bauernfeind F, Sterzik A, Orban M, Schnurr M, Lehr HA, Endres S, Eigler A, Dauer M. Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model. Gut 2007; 56:1275-82; PMID:17395611; http://dx.doi.org/10.1136/gut.2006.108621
   PubMed Web of Science ®Google Scholar
• Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331:1612-6; PMID:21436454; http://dx.doi.org/10.1126/science.1198443
   PubMed Web of Science ®Google Scholar
• Nowak AK, Robinson BW, Lake RA. Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. Cancer Res 2002; 62:2353-8; PMID:11956096
   PubMed Web of Science ®Google Scholar
• Nowak AK, Lake RA, Marzo AL, Scott B, Heath WR, Collins EJ, Frelinger JA, Robinson BW. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross tolerizing host tumor-specific CD8 T cells. J Immunol 2003; 170:4905-13; PMID:12734333; http://dx.doi.org/10.4049/jimmunol.170.10.4905
   PubMed Web of Science ®Google Scholar
• Plate JM, Plate AE, Shott S, Bograd S, Harris JE. Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas. Cancer Immunol Immunother 2005; 54:915-25; PMID:15782312; http://dx.doi.org/10.1007/s00262-004-0638-1
   PubMed Web of Science ®Google Scholar
• Yokoyama WM, Seaman W. The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex. Annu Rev Immunol 1993; 11:613; PMID:8476574; http://dx.doi.org/10.1146/annurev.iy.11.040193.003145
   PubMed Web of Science ®Google Scholar
• Ryan JC, Turck J, Niemi EC, Yokoyama WM, Seaman WE. Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules. J Immunol 1992; 149:1631; PMID:1506685
   PubMed Web of Science ®Google Scholar
• Ryan JC, Seaman WE. Divergent functions of lectin-like receptors on NK cells. Immunol Rev 1997; 155:79; PMID:9059884; http://dx.doi.org/10.1111/j.1600-065X.1997.tb00941.x
   PubMed Web of Science ®Google Scholar
• Carlyle JR, Martin A, Mehra A, Attisano L, Tsui FW, Zúñiga-Pflücker JC. Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function. J Immunol 1999; 162:5917; PMID:10229828
   PubMed Web of Science ®Google Scholar
• Kung SK, Su RC, Shannon J, Miller RG. The NKR-P1B gene product is an inhibitory receptor on SJL/J NK cells. J Immunol 1999; 162:5876; PMID:10229823
   PubMed Web of Science ®Google Scholar
• Koo GC, Dumont FJ, Tutt M, Hackett J Jr, Kumar V. The NK-1.12 mouse: a model to study differentiation of murine NK cells. J Immunol 1986; 137:3742; PMID:3782794
   PubMed Web of Science ®Google Scholar
• Arase H, Arase N, Saito T. Interferon-g production by natural killer (NK) cells and NK1.11 T cells upon NKR-P1 cross-linking. J Exp Med 1996; 183:2391; PMID:8642351; http://dx.doi.org/10.1084/jem.183.5.2391
   PubMed Web of Science ®Google Scholar
• Reichlin A, Yokoyama WM. Natural killer cell proliferation induced by anti-NK1.1 and IL-2. Immunol Cell Biol 1998; 76:143; PMID:9619484; http://dx.doi.org/10.1046/j.1440-1711.1998.00726.x
   PubMed Web of Science ®Google Scholar
• Assarsson E, Kambayashi T, Sandberg JK, Hong S, Taniguchi M, Van Kaer L, Ljunggren HG, Chambers BJ. CD8+ T cells rapidly acquire NK1.1 and NK cell-associated molecules upon stimulation in vitro and in vivo. J Immunol 2000; 165:3673-9; PMID:11034371; http://dx.doi.org/10.4049/jimmunol.165.7.3673
   PubMed Web of Science ®Google Scholar
• Kos FJ, Engleman EG. Role of natural killer cells in the generation of influenza virus-specific cytotoxic T cells. Cell Immunol 1996; 173:1; PMID:8871595; http://dx.doi.org/10.1006/cimm.1996.0245
   PubMed Web of Science ®Google Scholar
• Fergusson JR, Huhn MH, Swadling L, Walker LJ, Kurioka A, Llibre A, Bertoletti A, Holländer G, Newell EW, Davis MM et al. CD161intCD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut. Mucosal Immunol 2016; 9:401-13; PMID:26220166; http://dx.doi.org/10.1038/mi.2015.69
   PubMed Web of Science ®Google Scholar
• Billerbeck E, Kang Y-H, Walker L, Lockstone H, Grafmueller S, Fleming V, Flint J, Willberg CB, Bengsch B, Seigel B et al. Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA 2010; 107:3006-11; PMID:20133607; http://dx.doi.org/10.1073/pnas.0914839107
   PubMed Web of Science ®Google Scholar
• Fergusson JR, Fleming VM, Klenerman P. CD161-expressing human T-cells. Front Immunol 2011; 2:1-7; PMID:22566792; http://dx.doi.org/10.3389/fimmu.2011.00036
   PubMed Web of Science ®Google Scholar
• Northfield JW, Kasprowicz V, Lucas M, Kersting N, Bengsch B, Kim A, Phillips RE, Walker BD, Thimme R, Lauer G et al. CD161 expression on hepatitis C virus-specific CD8+ T cells suggests a distinct pathway of T cell differentiation. Hepatology 2008; 47:396-406; PMID:18219672; http://dx.doi.org/10.1002/hep.22040
   PubMed Web of Science ®Google Scholar
• Poon K, Montamat-Sicotte D, Cumberbatch N, McMichael AJ, Callan MF. Expression of leukocyte immunoglobulin-like receptors and natural killer receptors on virus-specific CD8+ T cells during the evolution of Epstein-Barr virus-specific immune responses in vivo. Viral Immunol 2005; 18:513-22; PMID:16212530; http://dx.doi.org/10.1089/vim.2005.18.513
   PubMed Web of Science ®Google Scholar