Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities
Tài liệu tham khảo
Rahib, 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, 10.1158/0008-5472.CAN-14-0155
Kleeff, 2016, Pancreatic cancer, Nat Rev Dis Primers, 2, 16022, 10.1038/nrdp.2016.22
Gabrilovich, 2009, Myeloid-derived suppressor cells as regulators of the immune system, Nat Rev Immunol, 9, 162, 10.1038/nri2506
Mantovani, 2017, Tumour-associated macrophages as treatment targets in oncology, Nat Rev Clin Oncol, 14, 399, 10.1038/nrclinonc.2016.217
Ugel, 2015, Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages, J Clin Invest, 125, 3365, 10.1172/JCI80006
Marvel, 2015, Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected, J Clin Invest, 125, 3356, 10.1172/JCI80005
Zhu, 2017, Tissue-resident macrophages in pancreatic ductal adenocarcinoma originate from embryonic hematopoiesis and promote tumor progression, Immunity, 47, 323, 10.1016/j.immuni.2017.07.014
Mitchem, 2013, Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses, Cancer Res, 73, 1128, 10.1158/0008-5472.CAN-12-2731
Bayne, 2012, Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer, Cancer Cell, 21, 822, 10.1016/j.ccr.2012.04.025
Rosati, 2015, BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages, Nat Commun, 6, 8695, 10.1038/ncomms9695
Pylayeva-Gupta, 2012, Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia, Cancer Cell, 21, 836, 10.1016/j.ccr.2012.04.024
Waghray, 2016, GM-CSF mediates mesenchymal-epithelial cross-talk in pancreatic cancer, Cancer Discov, 6, 886, 10.1158/2159-8290.CD-15-0947
Zhang, 2017, Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer, Gut, 66, 124, 10.1136/gutjnl-2016-312078
Beatty, 2015, Exclusion of T cells from pancreatic carcinomas in mice is regulated by Ly6C(low) F4/80(+) extratumoral macrophages, Gastroenterology, 149, 201, 10.1053/j.gastro.2015.04.010
Stromnes, 2014, Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity, Gut, 63, 1769, 10.1136/gutjnl-2013-306271
Seifert, 2016, Radiation therapy induces macrophages to suppress T-cell responses against pancreatic tumors in mice, Gastroenterology, 150, 1659, 10.1053/j.gastro.2016.02.070
Zhu, 2014, CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models, Cancer Res, 74, 5057, 10.1158/0008-5472.CAN-13-3723
Sanford, 2013, Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 Axis, Clin Cancer Res, 19, 3404, 10.1158/1078-0432.CCR-13-0525
Ino, 2013, Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer, Br J Cancer, 108, 914, 10.1038/bjc.2013.32
Takeuchi, 2015, Chemotherapy-derived inflammatory responses accelerate the formation of immunosuppressive myeloid cells in the tissue microenvironment of human pancreatic cancer, Cancer Res, 75, 2629, 10.1158/0008-5472.CAN-14-2921
Li, 2018, Tumor cell-intrinsic factors underlie heterogeneity of immune cell infiltration and response to immunotherapy, Immunity, 49, 178, 10.1016/j.immuni.2018.06.006
Balachandran, 2017, Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer, Nature, 551, 512, 10.1038/nature24462
Clark, 2007, Dynamics of the immune reaction to pancreatic cancer from inception to invasion, Cancer Res, 67, 9518, 10.1158/0008-5472.CAN-07-0175
Jang, 2017, Crosstalk between regulatory T cells and tumor-associated dendritic cells negates anti-tumor immunity in pancreatic cancer, Cell Rep, 20, 558, 10.1016/j.celrep.2017.06.062
Bengsch, 2017, CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer, Cancer Immunol Immunother, 66, 1609, 10.1007/s00262-017-2053-4
Liyanage, 2002, Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma, J Immunol, 169, 2756, 10.4049/jimmunol.169.5.2756
Hiraoka, 2006, Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions, Clin Cancer Res, 12, 5423, 10.1158/1078-0432.CCR-06-0369
McAllister, 2014, Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia, Cancer Cell, 25, 621, 10.1016/j.ccr.2014.03.014
Daley, 2016, Gammadelta T cells support pancreatic oncogenesis by restraining alphabeta T cell activation, Cell, 166, 1485, 10.1016/j.cell.2016.07.046
Gnerlich, 2010, Induction of Th17 cells in the tumor microenvironment improves survival in a murine model of pancreatic cancer, J Immunol, 185, 4063, 10.4049/jimmunol.0902609
Wu, 2015, Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines, J Exp Med, 212, 333, 10.1084/jem.20141702
Lee, 2016, Hif1a deletion reveals pro-neoplastic function of B cells in pancreatic neoplasia, Cancer Discov, 6, 256, 10.1158/2159-8290.CD-15-0822
Gunderson, 2016, Bruton tyrosine kinase-dependent immune cell cross-talk drives pancreas cancer, Cancer Discov, 6, 270, 10.1158/2159-8290.CD-15-0827
Pylayeva-Gupta, 2016, IL35-producing B cells promote the development of pancreatic neoplasia, Cancer Discov, 6, 247, 10.1158/2159-8290.CD-15-0843
Mace, 2013, Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner, Cancer Res, 73, 3007, 10.1158/0008-5472.CAN-12-4601
Kraman, 2010, Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha, Science, 330, 827, 10.1126/science.1195300
Feig, 2013, Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer, Proc Natl Acad Sci U S A, 110, 20212, 10.1073/pnas.1320318110
Ene-Obong, 2013, Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma, Gastroenterology, 145, 1121, 10.1053/j.gastro.2013.07.025
Rhim, 2014, Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma, Cancer Cell, 25, 735, 10.1016/j.ccr.2014.04.021
Ozdemir, 2014, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Cancer Cell, 25, 719, 10.1016/j.ccr.2014.04.005
Jiang, 2016, Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy, Nat Med, 22, 851, 10.1038/nm.4123
Seifert, 2016, The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression, Nature, 532, 245, 10.1038/nature17403
Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell, 21, 418, 10.1016/j.ccr.2012.01.007
Dougan, 2018, Targeting cytokine therapy to the pancreatic tumor microenvironment using PD-L1-specific VHHs, Cancer Immunol Res, 6, 389, 10.1158/2326-6066.CIR-17-0495
Thiriot, 2017, Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues, BMC Biol, 15, 45, 10.1186/s12915-017-0381-7
Motz, 2014, Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors, Nat Med, 20, 607, 10.1038/nm.3541
Mariathasan, 2018, TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells, Nature, 554, 544, 10.1038/nature25501
Liu, 2017, Use of angiotensin system inhibitors is associated with immune activation and longer survival in nonmetastatic pancreatic ductal adenocarcinoma, Clin Cancer Res, 23, 5959, 10.1158/1078-0432.CCR-17-0256
Kumar, 2016, Noninvasive assessment of losartan-induced increase in functional microvasculature and drug delivery in pancreatic ductal adenocarcinoma, Transl Oncol, 9, 431, 10.1016/j.tranon.2016.07.004
Chauhan, 2013, Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels, Nat Commun, 4, 2516, 10.1038/ncomms3516
Beatty, 2017, First-in-human phase I study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies, Clin Cancer Res, 23, 3269, 10.1158/1078-0432.CCR-16-2272
Maj, 2017, Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor, Nat Immunol, 18, 1332, 10.1038/ni.3868
Lyssiotis, 2017, Metabolic interactions in the tumor microenvironment, Trends Cell Biol, 27, 863, 10.1016/j.tcb.2017.06.003
Hingorani, 2005, Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice, Cancer Cell, 7, 469, 10.1016/j.ccr.2005.04.023
Hingorani, 2003, Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse, Cancer Cell, 4, 437, 10.1016/S1535-6108(03)00309-X
Lee, 2016, Genetically engineered mouse models of pancreatic cancer: the KPC model (LSL-KrasG12D/+;LSL-Trp53R172H/+ Pdx-1-Cre), its variants, and their application in immuno-oncology drug discovery, Curr Protoc Pharmacol, 73, 14.39.1, 10.1002/cpph.2
Tsujikawa, 2017, Quantitative multiplex immunohistochemistry reveals myeloid-inflamed tumor-immune complexity associated with poor prognosis, Cell Rep, 19, 203, 10.1016/j.celrep.2017.03.037
Carstens, 2017, Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer, Nat Commun, 8, 15095, 10.1038/ncomms15095
Stromnes, 2017, T-cell localization, activation, and clonal expansion in human pancreatic ductal adenocarcinoma, Cancer Immunol Res, 5, 978, 10.1158/2326-6066.CIR-16-0322
Beatty, 2017, Deploying immunotherapy in pancreatic cancer: defining mechanisms of response and resistance, Am Soc Clin Oncol Educ Book, 37, 267, 10.14694/EDBK_175232
Evans, 2016, Lack of immunoediting in murine pancreatic cancer reversed with neoantigen, JCI Insight, 1, e88328, 10.1172/jci.insight.88328
Bernhardt, 2006, Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study, Br J Cancer, 95, 1474, 10.1038/sj.bjc.6603437
Lepisto, 2008, 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, 6, 955
Capello, 2013, Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models, J Hematol Oncol, 6, 67, 10.1186/1756-8722-6-67
Oji, 2004, Overexpression of the Wilms’ tumor gene WT1 in pancreatic ductal adenocarcinoma, Cancer Sci, 95, 583, 10.1111/j.1349-7006.2004.tb02490.x
Takahara, 2011, Gemcitabine enhances Wilms’ tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune response, Cancer Immunol Immunother, 60, 1289, 10.1007/s00262-011-1033-3
Koido, 2014, Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms’ tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer, Clin Cancer Res, 20, 4228, 10.1158/1078-0432.CCR-14-0314
Johnston, 2009, Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer, Clin Cancer Res, 15, 6511, 10.1158/1078-0432.CCR-09-0565
Chen, 2014, Expansion of anti-mesothelin specific CD4+ and CD8+ T cell responses in patients with pancreatic carcinoma, PLoS One, 9, e88133, 10.1371/journal.pone.0088133
Thomas, 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, 10.1084/jem.20031435
Lutz, 2014, Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation, Cancer Immunol Res, 2, 616, 10.1158/2326-6066.CIR-14-0027
Le, 2015, Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer, J Clin Oncol, 33, 1325, 10.1200/JCO.2014.57.4244
Stromnes, 2015, T cells engineered against a native antigen can surmount immunologic and physical barriers to treat pancreatic ductal adenocarcinoma, Cancer Cell, 28, 638, 10.1016/j.ccell.2015.09.022
Wadle, 2006, Serological immune response to cancer testis antigens in patients with pancreatic cancer, Int J Cancer, 119, 117, 10.1002/ijc.21744
Abate-Daga, 2014, Development of a T cell receptor targeting an HLA-A*0201 restricted epitope from the cancer-testis antigen SSX2 for adoptive immunotherapy of cancer, PLoS One, 9, e93321, 10.1371/journal.pone.0093321
Schumacher, 2015, Neoantigens in cancer immunotherapy, Science, 348, 69, 10.1126/science.aaa4971
Biankin, 2012, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Nature, 491, 399, 10.1038/nature11547
Witkiewicz, 2015, Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets, Nat Commun, 6, 6744, 10.1038/ncomms7744
Balli, 2017, Immune cytolytic activity stratifies molecular subsets of human pancreatic cancer, Clin Cancer Res, 23, 3129, 10.1158/1078-0432.CCR-16-2128
Bailey, 2016, Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma, Sci Rep, 6, 35848, 10.1038/srep35848
Connor, 2017, Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma, JAMA Oncol, 3, 774, 10.1001/jamaoncol.2016.3916
Beatty, 2015, Immune escape mechanisms as a guide for cancer immunotherapy, Clin Cancer Res, 21, 687, 10.1158/1078-0432.CCR-14-1860
Vanneman, 2012, Combining immunotherapy and targeted therapies in cancer treatment, Nat Rev Cancer, 12, 237, 10.1038/nrc3237
Nywening, 2018, Targeting both tumour-associated CXCR2(+) neutrophils and CCR2(+) macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma, Gut, 67, 1112, 10.1136/gutjnl-2017-313738
Kumar, 2017, Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors, Cancer Cell, 32, 654, 10.1016/j.ccell.2017.10.005
Guerra, 2007, Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice, Cancer Cell, 11, 291, 10.1016/j.ccr.2007.01.012
Collins, 2012, Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice, J Clin Invest, 122, 639, 10.1172/JCI59227
Liou, 2013, Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-kappaB and MMPs, J Cell Biol, 202, 563, 10.1083/jcb.201301001
Zhu, 2014, Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit, Cancer Discov, 4, 452, 10.1158/2159-8290.CD-13-0646
Liou, 2017, The presence of interleukin-13 at pancreatic ADM/PanIN lesions alters macrophage populations and mediates pancreatic tumorigenesis, Cell Rep, 19, 1322, 10.1016/j.celrep.2017.04.052
Zhang, 2014, CD4+ T lymphocyte ablation prevents pancreatic carcinogenesis in mice, Cancer Immunol Res, 2, 423, 10.1158/2326-6066.CIR-14-0016-T
Kamerkar, 2017, Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer, Nature, 546, 498, 10.1038/nature22341
Pommier, 2018, Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases, Science, 360, eaao4908, 10.1126/science.aao4908
Sagiv-Barfi, 2018, Eradication of spontaneous malignancy by local immunotherapy, Sci Transl Med, 10, 10.1126/scitranslmed.aan4488
Fonseca, 2008, Capitalizing on the immunogenicity of dying tumor cells, Clin Cancer Res, 14, 1603, 10.1158/1078-0432.CCR-07-2245
Le, 2015, PD-1 blockade in tumors with mismatch-repair deficiency, N Engl J Med, 372, 2509, 10.1056/NEJMoa1500596
Chen, 2016, Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing, Nat Immunol, 17, 1142, 10.1038/ni.3558
Ochi, 2012, Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans, J Clin Invest, 122, 4118, 10.1172/JCI63606
Zambirinis, 2015, TLR9 ligation in pancreatic stellate cells promotes tumorigenesis, J Exp Med, 212, 2077, 10.1084/jem.20142162
Notta, 2016, A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns, Nature, 538, 378, 10.1038/nature19823
de Oliveira Mann, 2017, cGAS conducts micronuclei DNA surveillance, Trends Cell Biol, 27, 697, 10.1016/j.tcb.2017.08.007
Tauriello, 2018, TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis, Nature, 554, 538, 10.1038/nature25492
Vanpouille-Box, 2015, TGFbeta is a master regulator of radiation therapy-induced antitumor immunity, Cancer Res, 75, 2232, 10.1158/0008-5472.CAN-14-3511
Young, 2014, TGFbeta inhibition prior to hypofractionated radiation enhances efficacy in preclinical models, Cancer Immunol Res, 2, 1011, 10.1158/2326-6066.CIR-13-0207
Yasmin-Karim, 2018, Radiation and local anti-CD40 generate an effective in situ vaccine in preclinical models of pancreatic cancer, Front Immunol, 9, 2030, 10.3389/fimmu.2018.02030
Kalbasi, 2017, Tumor-derived CCL2 mediates resistance to radiotherapy in pancreatic ductal adenocarcinoma, Clin Cancer Res, 23, 137, 10.1158/1078-0432.CCR-16-0870
Rech, 2018, Radiotherapy and CD40 activation separately augment immunity to checkpoint blockade in cancer, Cancer Res, 78, 4282, 10.1158/0008-5472.CAN-17-3821
Twyman-Saint Victor, 2015, Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer, Nature, 520, 373, 10.1038/nature14292
Rudqvist, 2018, Radiotherapy and CTLA-4 blockade shape the TCR repertoire of tumor-infiltrating T cells, Cancer Immunol Res, 6, 139, 10.1158/2326-6066.CIR-17-0134
Dougan, 2018, Regulation of innate and adaptive antitumor immunity by IAP antagonists, Immunotherapy, 10, 787, 10.2217/imt-2017-0185
Clancy-Thompson, 2018, IAP antagonists enhance cytokine production from mouse and human iNKT cells, Cancer Immunol Res, 6, 25, 10.1158/2326-6066.CIR-17-0490
Dougan, 2010, IAP inhibitors enhance co-stimulation to promote tumor immunity, J Exp Med, 207, 2195, 10.1084/jem.20101123
Beatty, 2017, Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists, Expert Rev Anticancer Ther, 17, 175, 10.1080/14737140.2017.1270208
Beatty, 2011, CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans, Science, 331, 1612, 10.1126/science.1198443
Beatty, 2013, A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma, Clin Cancer Res, 19, 6286, 10.1158/1078-0432.CCR-13-1320
Long, 2016, IFNgamma and CCL2 cooperate to redirect tumor-infiltrating monocytes to degrade fibrosis and enhance chemotherapy efficacy in pancreatic carcinoma, Cancer Discov, 6, 400, 10.1158/2159-8290.CD-15-1032
Byrne, 2016, CD40 stimulation obviates innate sensors and drives T cell immunity in cancer, Cell Rep, 15, 2719, 10.1016/j.celrep.2016.05.058
Beatty, 2016, Chimeric antigen receptor-modified T cells for the treatment of solid tumors: defining the challenges and next steps, Pharmacol Ther, 166, 30, 10.1016/j.pharmthera.2016.06.010
Chmielewski, 2012, T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice, Gastroenterology, 143, 1095, 10.1053/j.gastro.2012.06.037
Maliar, 2012, Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice, Gastroenterology, 143, 1375, 10.1053/j.gastro.2012.07.017
Watanabe, 2018, Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses, JCI Insight, 3, e99573, 10.1172/jci.insight.99573
Heckler, 2018, Unmasking pancreatic cancer: epitope spreading after single antigen chimeric antigen receptor T-cell therapy in a human phase I trial, Gastroenterology, 155, 11, 10.1053/j.gastro.2018.06.023
Franklin, 2014, The cellular and molecular origin of tumor-associated macrophages, Science, 344, 921, 10.1126/science.1252510
Nywening, 2016, Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial, Lancet Oncol, 17, 651, 10.1016/S1470-2045(16)00078-4
Steele, 2016, CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma, Cancer Cell, 29, 832, 10.1016/j.ccell.2016.04.014
Dranoff, 2004, Cytokines in cancer pathogenesis and cancer therapy, Nat Rev Cancer, 4, 11, 10.1038/nrc1252
Wang, 2017, Re-designing interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent, Nat Commun, 8, 1395, 10.1038/s41467-017-01385-8
Ohlund, 2017, Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer, J Exp Med, 214, 579, 10.1084/jem.20162024
Long, 2017, IL-6 receptor blockade enhances chemotherapy efficacy in pancreatic ductal adenocarcinoma, Mol Cancer Ther, 16, 1898, 10.1158/1535-7163.MCT-16-0899
Mace, 2016, IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer, Gut, 67, 320, 10.1136/gutjnl-2016-311585
Jiang, 2017, Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy, Cancer Immunol Immunother, 66, 1037, 10.1007/s00262-017-2003-1
Jacobetz, 2013, Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer, Gut, 62, 112, 10.1136/gutjnl-2012-302529
Sharma, 2017, Primary, adaptive, and acquired resistance to cancer immunotherapy, Cell, 168, 707, 10.1016/j.cell.2017.01.017
Rooney, 2015, Molecular and genetic properties of tumors associated with local immune cytolytic activity, Cell, 160, 48, 10.1016/j.cell.2014.12.033
Brooks, 2018, Perioperative, spatiotemporally coordinated activation of T and NK cells prevents recurrence of pancreatic cancer, Cancer Res, 78, 475, 10.1158/0008-5472.CAN-17-2415
Gurlevik, 2016, Administration of gemcitabine after pancreatic tumor resection in mice induces an antitumor immune response mediated by natural killer cells, Gastroenterology, 151, 338, 10.1053/j.gastro.2016.05.004
Howitt, 2016, Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut, Science, 351, 1329, 10.1126/science.aaf1648
Westphalen, 2016, Dclk1 defines quiescent pancreatic progenitors that promote injury-induced regeneration and tumorigenesis, Cell Stem Cell, 18, 441, 10.1016/j.stem.2016.03.016
Bailey, 2014, DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer, Gastroenterology, 146, 245, 10.1053/j.gastro.2013.09.050
Zhang, 2018, Immune cell production of interleukin 17 induces stem cell features of pancreatic intraepithelial neoplasia cells, Gastroenterology, 155, 210, 10.1053/j.gastro.2018.03.041
Brahmer, 2012, Safety and activity of anti-PD-L1 antibody in patients with advanced cancer, N Engl J Med, 366, 2455, 10.1056/NEJMoa1200694
Royal, 2010, Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma, J Immunother, 33, 828
Naing, 2018, Abstract CT177: epacadostat plus durvalumab in patients with advanced solid tumors: preliminary results of the ongoing, open-label, phase I/II ECHO-203 study, Cancer Res, 78, CT177, 10.1158/1538-7445.AM2018-CT177
Zitvogel, 2008, Immunological aspects of cancer chemotherapy, Nat Rev Immunol, 8, 59, 10.1038/nri2216
Pfirschke, 2016, Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy, Immunity, 44, 343, 10.1016/j.immuni.2015.11.024
Aglietta, 2014, A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer, Ann Oncol, 25, 1750, 10.1093/annonc/mdu205
Von Hoff, 2011, Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial, J Clin Oncol, 29, 4548, 10.1200/JCO.2011.36.5742
Conroy, 2011, FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer, N Engl J Med, 364, 1817, 10.1056/NEJMoa1011923
Coveler, 2016, Algenpantucel-L immunotherapy in pancreatic adenocarcinoma, Immunotherapy, 8, 117, 10.2217/imt.15.113
Le, 2017, Results from a phase 2b, randomized, multicenter study of GVAX pancreas and CRS-207 compared to chemotherapy in adults with previously-treated metastatic pancreatic adenocarcinoma (ECLIPSE Study), J Clin Oncol, 35, 10.1200/JCO.2017.35.4_suppl.345
Middleton, 2014, Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial, Lancet Oncol, 15, 829, 10.1016/S1470-2045(14)70236-0
Ercolini, 2005, Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response, J Exp Med, 201, 1591, 10.1084/jem.20042167
Laheru, 2008, Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation, Clin Cancer Res, 14, 1455, 10.1158/1078-0432.CCR-07-0371
Chen, 2013, Oncology meets immunology: the cancer-immunity cycle, Immunity, 39, 1, 10.1016/j.immuni.2013.07.012
Beatty, 2018, Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial, Gastroenterology, 155, 29, 10.1053/j.gastro.2018.03.029
Beatty, 2014, Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce antitumor activity in solid malignancies, Cancer Immunol Res, 2, 112, 10.1158/2326-6066.CIR-13-0170
Beatty, 2014, Chimeric antigen receptor T cells are vulnerable to immunosuppressive mechanisms present within the tumor microenvironment, Oncoimmunology, 3, e970027, 10.4161/21624011.2014.970027
Le, 2017, Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade, Science, 357, 409, 10.1126/science.aan6733
Carleton, 2018, Pharmacodynamics (PD) and genomic profiling of pts treated with cabiralizumab (cabira) + nivolumab (NIVO) provide evidence of on-target tumor immune modulations and support future clinical applications, J Clin Oncol, 36, 10.1200/JCO.2018.36.15_suppl.3020
Wainberg, 2017, First-in-human phase 1 dose escalation and expansion of a novel combination, anti–CSF-1 receptor (cabiralizumab) plus anti–PD-1 (nivolumab), in patients with advanced solid tumors, J Immunother Cancer, 5, O42
Lupinacci, 2017, Prevalence of microsatellite instability in intraductal papillary mucinous neoplasms of the pancreas, Gastroenterology, 154, 1061, 10.1053/j.gastro.2017.11.009
Bahary, 2018, Phase 2 trial of the IDO pathway inhibitor indoximod plus gemcitabine / nab-paclitaxel for the treatment of patients with metastatic pancreas cancer, J Clin Oncol, 36, 4015, 10.1200/JCO.2018.36.15_suppl.4015
Nowak, 2003, Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors, Cancer Res, 63, 4490
Obeid, 2007, Calreticulin exposure dictates the immunogenicity of cancer cell death, Nat Med, 13, 54, 10.1038/nm1523
Brenchley, 2003, Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells, Blood, 101, 2711, 10.1182/blood-2002-07-2103
Cioffi, 2015, Inhibition of CD47 effectively targets pancreatic cancer stem cells via dual mechanisms, Clin Cancer Res, 21, 2325, 10.1158/1078-0432.CCR-14-1399
Willingham, 2012, The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors, Proc Natl Acad Sci U S A, 109, 6662, 10.1073/pnas.1121623109
Antonia, 2017, Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer, N Engl J Med, 377, 1919, 10.1056/NEJMoa1709937
Brahmer, 2018, Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline, J Clin Oncol, 36, 1714, 10.1200/JCO.2017.77.6385
Reynolds, 2018, Diagnosis and management of hepatitis in patients on checkpoint blockade, Oncologist, 23, 991, 10.1634/theoncologist.2018-0174
Dougan, 2017, Checkpoint blockade toxicity and immune homeostasis in the gastrointestinal tract, Front Immunol, 8, 1547, 10.3389/fimmu.2017.01547
Ferrara, 2018, Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with PD-1/PD-l1 inhibitors or with single-agent chemotherapy, JAMA Oncol, 4, 1543, 10.1001/jamaoncol.2018.3676
Rahib, 2016, Evaluation of pancreatic cancer clinical trials and benchmarks for clinically meaningful future trials: a systematic review, JAMA Oncol, 2, 1209, 10.1001/jamaoncol.2016.0585