CoChat
Sign Up
Cited by 106Immune cells in cancerPancreatic and Hepatic Oncology ResearchCancer Cells and Metastasis

Tumor-associated macrophages in pancreatic ductal adenocarcinoma: therapeutic opportunities and clinical challenges

Open access
Poh, Ashleigh R., Ernst, Matthias·2021·Cancers
DOI 10.3390/cancers13122860PMC PMC8226457
Open this paper in CoChat — free accountOpen PDF

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a 5-year survival rate of less than 10%. Macrophages are one of the earliest infiltrating cells in the pancreatic tumor microenvironment, and are associated with an increased risk of disease progression, recurrence, metastasis, and shorter overall survival. Pre-clinical studies have demonstrated an unequivocal role of macrophages in PDAC by contributing to chronic inflammation, cancer cell stemness, desmoplasia, immune suppression, angiogenesis, invasion, metastasis, and drug resistance. Several macrophage-targeting therapies have also been investigated in pre-clinical models, and include macrophage depletion, inhibiting macrophage recruitment, and macrophage reprogramming. However, the effectiveness of these drugs in pre-clinical models has not always translated into clinical trials. In this review, we discuss the molecular mechanisms that underpin macrophage heterogeneity within the pancreatic tumor microenvironment, and examine the contribution of macrophages at various stages of PDAC progression. We also provide a comprehensive update of macrophage-targeting therapies that are currently undergoing clinical evaluation, and discuss clinical challenges associated with these treatment modalities in human PDAC patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/cancers13122860

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The high-density stroma of PDAC, comprised of CAFs, adipocytes, immune cells, ECs, nerve cells, PSCs, and ECM components like collagen and hyaluronic acid, constitutes up to 90% of tumor volume.

    “The high-density stroma of PDAC, comprised of cancer-associated fibroblasts (CAFs), adipocytes, immune cells, ECs, nerve cells, pancreatic stellate cells (PSCs), and extracellular matrix components (ECM) like collagen and hyaluronic acid, constitutes up to 90% of the tumor volume (Jacobetz et al., 2013; Poh and Ernst, 2021; Wu et al., 2021).”

    From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Poh and Ernst, 2021

    The Introduction describes dense PDAC stroma containing fibroblasts, stellate cells, immune cells, endothelial cells, collagen, and hyaluronic acid. It says the stroma can account for up to 80% of tumor mass, not 90%, and does not list adipocytes or nerve cells among its components. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Increased density of macrophages in the tumor serves as an independent prognostic factor in PDAC patients, correlating with elevated risk of disease progression, recurrence, metastasis, and reduced overall survival.

    “Notably, an increased density of macrophages in the tumor serves as an independent prognostic factor in PDAC patients, correlating with an elevated risk of disease progression, recurrence, metastasis, and reduced overall survival (Poh and Ernst, 2021).”

    From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Poh and Ernst, 2021

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 223 · Cited by 106

Research works printed but not linked: 197

  1. [1]Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2020 CA Cancer J. Clin. 2020 70 7 30 10.3322/caac.21590 31912902 · DOI · Paper page
  2. [4]Adamska A. Domenichini A. Falasca M. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies Int. J. Mol. Sci. 2017 18 1338 10.3390/ijms18071338 28640192 PMC5535831 · DOI
  3. [5]Conroy T. Desseigne F. Ychou M. Bouche O. Guimbaud R. Becouarn Y. Adenis A. Raoul J.L. Gourgou-Bourgade S. de la Fouchardiere C. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer N. Engl. J. Med. 2011 364 1817 1825 10.1056/NEJMoa1011923 21561347 · DOI · Paper page
  4. [6]Von Hoff D.D. Ervin T. Arena F.P. Chiorean E.G. Infante J. Moore M. Seay T. Tjulandin S.A. Ma W.W. Saleh M.N. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine N. Engl. J. Med. 2013 369 1691 1703 10.1056/NEJMoa1304369 24131140 PMC4631139 · DOI · Paper page
  5. [7]Hidalgo M. Cascinu S. Kleeff J. Labianca R. Lohr J.M. Neoptolemos J. Real F.X. Van Laethem J.L. Heinemann V. Addressing the challenges of pancreatic cancer: Future directions for improving outcomes Pancreatology 2015 15 8 18 10.1016/j.pan.2014.10.001 25547205 · DOI
  6. [8]Barugola G. Partelli S. Marcucci S. Sartori N. Capelli P. Bassi C. Pederzoli P. Falconi M. Resectable pancreatic cancer: Who really benefits from resection? Ann. Surg. Oncol. 2009 16 3316 3322 10.1245/s10434-009-0670-7 19707831 · DOI
  7. [9]Hishinuma S. Ogata Y. Tomikawa M. Ozawa I. Hirabayashi K. Igarashi S. Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings J. Gastrointest. Surg. 2006 10 511 518 10.1016/j.gassur.2005.09.016 16627216 · DOI
  8. [10]Chu G.C. Kimmelman A.C. Hezel A.F. DePinho R.A. Stromal biology of pancreatic cancer J. Cell. Biochem. 2007 101 887 907 10.1002/jcb.21209 17266048 · DOI
  9. [11]Erkan M. Hausmann S. Michalski C.W. Fingerle A.A. Dobritz M. Kleeff J. Friess H. The role of stroma in pancreatic cancer: Diagnostic and therapeutic implications Nat. Rev. Gastroenterol. Hepatol. 2012 9 454 467 10.1038/nrgastro.2012.115 22710569 · DOI · Paper page
  10. [12]Provenzano P.P. Hingorani S.R. Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer Br. J. Cancer 2013 108 1 8 10.1038/bjc.2012.569 23299539 PMC3553539 · DOI
  11. [13]Wörmann S.M. Diakopoulos K.N. Lesina M. Algül H. The immune network in pancreatic cancer development and progression Oncogene 2014 33 2956 2967 10.1038/onc.2013.257 23851493 · DOI
  12. [14]Clark C.E. Hingorani S.R. Mick R. Combs C. Tuveson D.A. Vonderheide R.H. Dynamics of the immune reaction to pancreatic cancer from inception to invasion Cancer Res. 2007 67 9518 9527 10.1158/0008-5472.CAN-07-0175 17909062 · DOI · Paper page
  13. [15]Beatty G.L. Eghbali S. Kim R. Deploying Immunotherapy in Pancreatic Cancer: Defining Mechanisms of Response and Resistance Am. Soc. Clin. Oncol. Educ. Book 2017 37 267 278 10.1200/EDBK_175232 28561678 · DOI
  14. [16]Yu M. Guan R. Hong W. Zhou Y. Lin Y. Jin H. Hou B. Jian Z. Prognostic value of tumor-associated macrophages in pancreatic cancer: A meta-analysis Cancer Manag. Res. 2019 11 4041 4058 10.2147/CMAR.S196951 31118813 PMC6504556 · DOI
  15. [17]Zhu Y. Herndon J.M. Sojka D.K. Kim K.W. Knolhoff B.L. Zuo C. Cullinan D.R. Luo J. Bearden A.R. Lavine K.J. Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression Immunity 2017 47 323 338.e326 10.1016/j.immuni.2017.07.014 28813661 PMC5578409 · DOI
  16. [18]Nywening T.M. Belt B.A. Cullinan D.R. Panni R.Z. Han B.J. Sanford D.E. Jacobs R.C. Ye J. Patel A.A. Gillanders W.E. Targeting both tumour-associated CXCR2+ neutrophils and CCR2+ macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma Gut 2018 67 1112 1123 10.1136/gutjnl-2017-313738 29196437 PMC5969359 · DOI
  17. [19]Kalbasi A. Komar C. Tooker G.M. Liu M. Lee J.W. Gladney W.L. Ben-Josef E. Beatty G.L. Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2017 23 137 148 10.1158/1078-0432.CCR-16-0870 27354473 PMC5195913 · DOI
  18. [20]Mitchem J.B. Brennan D.J. Knolhoff B.L. Belt B.A. Zhu Y. Sanford D.E. Belaygorod L. Carpenter D. Collins L. Piwnica-Worms D. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses Cancer Res. 2013 73 1128 1141 10.1158/0008-5472.CAN-12-2731 23221383 PMC3563931 · DOI
  19. [21]Sanford D.E. Belt B.A. Panni R.Z. Mayer A. Deshpande A.D. Carpenter D. Mitchem J.B. Plambeck-Suess S.M. Worley L.A. Goetz B.D. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: A role for targeting the CCL2/CCR2 axis Clin. Cancer Res. 2013 19 3404 3415 10.1158/1078-0432.CCR-13-0525 23653148 PMC3700620 · DOI
  20. [22]Calderon B. Carrero J.A. Ferris S.T. Sojka D.K. Moore L. Epelman S. Murphy K.M. Yokoyama W.M. Randolph G.J. Unanue E.R. The pancreas anatomy conditions the origin and properties of resident macrophages J. Exp. Med. 2015 212 1497 1512 10.1084/jem.20150496 26347472 PMC4577842 · DOI · Paper page
  21. [23]Beatty G.L. Winograd R. Evans R.A. Long K.B. Luque S.L. Lee J.W. Clendenin C. Gladney W.L. Knoblock D.M. Guirnalda P.D. Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6Clow F4/80+ Extratumoral Macrophages Gastroenterology 2015 149 201 210 10.1053/j.gastro.2015.04.010 25888329 PMC4478138 · DOI
  22. [24]Poh A.R. Ernst M. Targeting Macrophages in Cancer: From Bench to Bedside Front. Oncol. 2018 8 49 10.3389/fonc.2018.00049 29594035 PMC5858529 · DOI
  23. [25]Murray P.J. Allen J.E. Biswas S.K. Fisher E.A. Gilroy D.W. Goerdt S. Gordon S. Hamilton J.A. Ivashkiv L.B. Lawrence T. Macrophage activation and polarization: Nomenclature and experimental guidelines Immunity 2014 41 14 20 10.1016/j.immuni.2014.06.008 25035950 PMC4123412 · DOI · Paper page
  24. [26]Biswas S.K. Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm Nat. Immunol. 2010 11 889 896 10.1038/ni.1937 20856220 · DOI · Paper page
  25. [27]Mosser D. Edwards J. Exploring the full spectrum of macrophage activation Nat. Rev. Immunol. 2008 8 958 969 10.1038/nri2448 19029990 PMC2724991 · DOI · Paper page
  26. [28]Sica A. Larghi P. Mancino A. Rubino L. Porta C. Totaro M. Rimoldi M. Biswas S. Allavena P. Mantovani A. Macrophage polarisation in tumour progression Semin. Cancer Biol. 2008 18 349 355 10.1016/j.semcancer.2008.03.004 18467122 · DOI · Paper page
  27. [29]Martinez F.O. Gordon S. Locati M. Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: New molecules and patterns of gene expression J. Immunol. 2006 177 7303 7311 10.4049/jimmunol.177.10.7303 17082649 · DOI
  28. [30]Abdelaziz M.H. Abdelwahab S.F. Wan J. Cai W. Huixuan W. Jianjun C. Kumar K.D. Vasudevan A. Sadek A. Su Z. Alternatively activated macrophages; a double-edged sword in allergic asthma J. Transl. Med. 2020 18 58 10.1186/s12967-020-02251-w 32024540 PMC7003359 · DOI
  29. [31]Wang L.-X. Zhang S.-X. Wu H.-J. Rong X.-L. Guo J. M2b macrophage polarization and its roles in diseases J. Leukoc. Biol. 2019 106 345 358 10.1002/JLB.3RU1018-378RR 30576000 PMC7379745 · DOI
  30. [32]Zizzo G. Hilliard B.A. Monestier M. Cohen P.L. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction J. Immunol. 2012 189 3508 3520 10.4049/jimmunol.1200662 22942426 PMC3465703 · DOI
  31. [33]Wang Q. Ni H. Lan L. Wei X. Xiang R. Wang Y. Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages Cell Res. 2010 20 701 712 10.1038/cr.2010.52 20386569 · DOI
  32. [34]Ferrante C.J. Pinhal-Enfield G. Elson G. Cronstein B.N. Hasko G. Outram S. Leibovich S.J. The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Rα) signaling Inflammation 2013 36 921 931 10.1007/s10753-013-9621-3 23504259 PMC3710311 · DOI · Paper page
  33. [35]Lewis C.E. Pollard J.W. Distinct role of macrophages in different tumor microenvironments Cancer Res. 2006 66 605 612 10.1158/0008-5472.CAN-05-4005 16423985 · DOI · Paper page
  34. [36]Tekin C. Aberson H.L. Bijlsma M.F. Spek C.A. Early macrophage infiltrates impair pancreatic cancer cell growth by TNF-α secretion BMC Cancer 2020 20 1183 10.1186/s12885-020-07697-1 33267818 PMC7709323 · DOI
  35. [37]Liou G.-Y. Döppler H. Necela B. Krishna M. Crawford H.C. Raimondo M. Storz P. Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs J. Cell Biol. 2013 202 563 577 10.1083/jcb.201301001 23918941 PMC3734091 · DOI
  36. [38]Liou G.Y. Döppler H. Necela B. Edenfield B. Zhang L. Dawson D.W. Storz P. Mutant KRAS-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions Cancer Discov. 2015 5 52 63 10.1158/2159-8290.CD-14-0474 25361845 PMC4293204 · DOI
  37. [39]Griesmann H. Drexel C. Milosevic N. Sipos B. Rosendahl J. Gress T.M. Michl P. Pharmacological macrophage inhibition decreases metastasis formation in a genetic model of pancreatic cancer Gut 2017 66 1278 1285 10.1136/gutjnl-2015-310049 27013602 · DOI
  38. [40]Penny H.L. Sieow J.L. Adriani G. Yeap W.H. See Chi Ee P. San Luis B. Lee B. Lee T. Mak S.Y. Ho Y.S. Warburg metabolism in tumor-conditioned macrophages promotes metastasis in human pancreatic ductal adenocarcinoma Oncoimmunology 2016 5 e1191731 10.1080/2162402X.2016.1191731 27622062 PMC5007961 · DOI
  39. [41]Kimsey T.F. Campbell A.S. Albo D. Wilson M. Wang T.N. Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion Cancer J. 2004 10 374 380 10.1097/00130404-200411000-00007 15701269 · DOI
  40. [42]Kleeff J. Kusama T. Rossi D.L. Ishiwata T. Maruyama H. Friess H. Büchler M.W. Zlotnik A. Korc M. Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer Int. J. Cancer 1999 81 650 657 10.1002/(SICI)1097-0215(19990517)81:4<650::AID-IJC23>3.0.CO;2-# 10225458 · DOI
  41. [43]Campbell A.S. Albo D. Kimsey T.F. White S.L. Wang T.N. Macrophage inflammatory protein-3alpha promotes pancreatic cancer cell invasion J. Surg. Res. 2005 123 96 101 10.1016/j.jss.2004.07.013 15652956 · DOI
  42. [44]Liu B. Jia Y. Ma J. Wu S. Jiang H. Cao Y. Sun X. Yin X. Yan S. Shang M. Tumor-associated macrophage-derived CCL20 enhances the growth and metastasis of pancreatic cancer Acta Biochim. Biophys. Sin. 2016 48 1067 1074 10.1093/abbs/gmw101 27797715 · DOI
  43. [45]Farrow B. Evers B.M. Inflammation and the development of pancreatic cancer Surg. Oncol. 2002 10 153 169 10.1016/S0960-7404(02)00015-4 12020670 · DOI · Paper page
  44. [46]Stone M.L. Beatty G.L. Cellular determinants and therapeutic implications of inflammation in pancreatic cancer Pharmacol. Ther. 2019 201 202 213 10.1016/j.pharmthera.2019.05.012 31158393 PMC6708742 · DOI
  45. [47]Kirkegård J. Mortensen F.V. Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis Am. J. Gastroenterol. 2017 112 1366 1372 10.1038/ajg.2017.218 28762376 · DOI
  46. [48]Midha S. Chawla S. Garg P.K. Modifiable and non-modifiable risk factors for pancreatic cancer: A review Cancer Lett. 2016 381 269 277 10.1016/j.canlet.2016.07.022 27461582 · DOI
  47. [50]Korc M. Jeon C.Y. Edderkaoui M. Pandol S.J. Petrov M.S. Tobacco and alcohol as risk factors for pancreatic cancer Best Pract. Res. Clin. Gastroenterol. 2017 31 529 536 10.1016/j.bpg.2017.09.001 29195672 PMC5747325 · DOI
  48. [51]Anderson M.A. Zolotarevsky E. Cooper K.L. Sherman S. Shats O. Whitcomb D.C. Lynch H.T. Ghiorzo P. Rubinstein W.S. Vogel K.J. Alcohol and tobacco lower the age of presentation in sporadic pancreatic cancer in a dose-dependent manner: A multicenter study Am. J. Gastroenterol. 2012 107 1730 1739 10.1038/ajg.2012.288 22929760 PMC3923585 · DOI · Paper page
  49. [52]Dugernier T.L. Laterre P.F. Wittebole X. Roeseler J. Latinne D. Reynaert M.S. Pugin J. Compartmentalization of the inflammatory response during acute pancreatitis: Correlation with local and systemic complications Am. J. Respir. Crit. Care Med. 2003 168 148 157 10.1164/rccm.2204019 12851244 · DOI
  50. [53]Perides G. Weiss E.R. Michael E.S. Laukkarinen J.M. Duffield J.S. Steer M.L. TNF-alpha-dependent regulation of acute pancreatitis severity by Ly-6C(hi) monocytes in mice J. Biol. Chem. 2011 286 13327 13335 10.1074/jbc.M111.218388 21343291 PMC3075679 · DOI
  51. [54]Shamoon M. Deng Y. Chen Y.Q. Bhatia M. Sun J. Therapeutic implications of innate immune system in acute pancreatitis Expert Opin. Ther. Targets 2016 20 73 87 10.1517/14728222.2015.1077227 26565751 · DOI
  52. [55]Xue J. Sharma V. Hsieh M.H. Chawla A. Murali R. Pandol S.J. Habtezion A. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis Nat. Commun. 2015 6 7158 10.1038/ncomms8158 25981357 PMC4632846 · DOI
  53. [56]Storz P. Acinar cell plasticity and development of pancreatic ductal adenocarcinoma Nat. Rev. Gastroenterol. Hepatol. 2017 14 296 304 10.1038/nrgastro.2017.12 28270694 PMC6036907 · DOI
  54. [57]Song S.Y. Gannon M. Washington M.K. Scoggins C.R. Meszoely I.M. Goldenring J.R. Marino C.R. Sandgren E.P. Coffey R.J. Jr. Wright C.V. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha Gastroenterology 1999 117 1416 1426 10.1016/S0016-5085(99)70292-1 10579983 · DOI
  55. [58]Stanger B.Z. Hebrok M. Control of cell identity in pancreas development and regeneration Gastroenterology 2013 144 1170 1179 10.1053/j.gastro.2013.01.074 23622126 PMC3639438 · DOI
  56. [59]Hingorani S.R. Wang L. Multani A.S. Combs C. Deramaudt T.B. Hruban R.H. Rustgi A.K. Chang S. Tuveson D.A. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice Cancer Cell 2005 7 469 483 10.1016/j.ccr.2005.04.023 15894267 · DOI · Paper page
  57. [60]Lee J.W. Komar C.A. Bengsch F. Graham K. Beatty G.L. 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. 2016 73 14 39 10.1002/cpph.2 27248578 PMC4915217 · DOI
  58. [62]Ray K.C. Moss M.E. Franklin J.L. Weaver C.J. Higginbotham J. Song Y. Revetta F.L. Blaine S.A. Bridges L.R. Guess K.E. Heparin-binding epidermal growth factor-like growth factor eliminates constraints on activated Kras to promote rapid onset of pancreatic neoplasia Oncogene 2014 33 823 831 10.1038/onc.2013.3 23376846 PMC3929321 · DOI
  59. [63]Kumar S. Torres M.P. Kaur S. Rachagani S. Joshi S. Johansson S.L. Momi N. Baine M.J. Gilling C.E. Smith L.M. Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages Oncogene 2015 34 2052 2060 10.1038/onc.2014.154 24909166 PMC4457293 · DOI
  60. [64]Liou G.-Y. Bastea L. Fleming A. Döppler H. Edenfield B.H. Dawson D.W. Zhang L. Bardeesy N. Storz P. The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis Cell Rep. 2017 19 1322 1333 10.1016/j.celrep.2017.04.052 28514653 PMC5510483 · DOI
  61. [66]Guerra C. Schuhmacher A.J. Cañamero M. Grippo P.J. Verdaguer L. Pérez-Gallego L. Dubus P. Sandgren E.P. Barbacid M. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice Cancer Cell 2007 11 291 302 10.1016/j.ccr.2007.01.012 17349585 · DOI · Paper page
  62. [67]Rhim A.D. Mirek E.T. Aiello N.M. Maitra A. Bailey J.M. McAllister F. Reichert M. Beatty G.L. Rustgi A.K. Vonderheide R.H. EMT and dissemination precede pancreatic tumor formation Cell 2012 148 349 361 10.1016/j.cell.2011.11.025 22265420 PMC3266542 · DOI · Paper page
  63. [68]Rhim A.D. Thege F.I. Santana S.M. Lannin T.B. Saha T.N. Tsai S. Maggs L.R. Kochman M.L. Ginsberg G.G. Lieb J.G. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions Gastroenterology 2014 146 647 651 10.1053/j.gastro.2013.12.007 24333829 PMC4514438 · DOI
  64. [70]Di Carlo C. Brandi J. Cecconi D. Pancreatic cancer stem cells: Perspectives on potential therapeutic approaches of pancreatic ductal adenocarcinoma World J. Stem Cells 2018 10 172 182 10.4252/wjsc.v10.i11.172 30631392 PMC6325076 · DOI
  65. [71]Valle S. Martin-Hijano L. Alcalá S. Alonso-Nocelo M. Sainz B. Jr. The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer Cancers 2018 10 33 10.3390/cancers10020033 PMC5836065 29373514 · DOI
  66. [72]Hou Y.C. Chao Y.J. Tung H.L. Wang H.C. Shan Y.S. Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma Cancer 2014 120 2766 2777 10.1002/cncr.28774 24839953 PMC4232049 · DOI
  67. [73]Sainz B. Jr. Martín B. Tatari M. Heeschen C. Guerra S. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells Cancer Res. 2014 74 7309 7320 10.1158/0008-5472.CAN-14-1354 25368022 · DOI
  68. [74]Sainz B. Jr. Alcala S. Garcia E. Sanchez-Ripoll Y. Azevedo M.M. Cioffi M. Tatari M. Miranda-Lorenzo I. Hidalgo M. Gomez-Lopez G. Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment Gut 2015 64 1921 1935 10.1136/gutjnl-2014-308935 25841238 · DOI
  69. [75]Phillips P.A. McCarroll J.A. Park S. Wu M.J. Pirola R. Korsten M. Wilson J.S. Apte M.V. Rat pancreatic stellate cells secrete matrix metalloproteinases: Implications for extracellular matrix turnover Gut 2003 52 275 282 10.1136/gut.52.2.275 12524413 PMC1774949 · DOI
  70. [76]Apte M.V. Haber P.S. Darby S.J. Rodgers S.C. McCaughan G.W. Korsten M.A. Pirola R.C. Wilson J.S. Pancreatic stellate cells are activated by proinflammatory cytokines: Implications for pancreatic fibrogenesis Gut 1999 44 534 541 10.1136/gut.44.4.534 10075961 PMC1727467 · DOI
  71. [77]Mews P. Phillips P. Fahmy R. Korsten M. Pirola R. Wilson J. Apte M. Pancreatic stellate cells respond to inflammatory cytokines: Potential role in chronic pancreatitis Gut 2002 50 535 541 10.1136/gut.50.4.535 11889076 PMC1773172 · DOI
  72. [78]Schneider E. Schmid-Kotsas A. Zhao J. Weidenbach H. Schmid R.M. Menke A. Adler G. Waltenberger J. Grünert A. Bachem M.G. Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells Am. J. Physiol. Cell Physiol. 2001 281 C532 C543 10.1152/ajpcell.2001.281.2.C532 11443052 · DOI
  73. [79]Bachem M.G. Schünemann M. Ramadani M. Siech M. Beger H. Buck A. Zhou S. Schmid-Kotsas A. Adler G. Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells Gastroenterology 2005 128 907 921 10.1053/j.gastro.2004.12.036 15825074 · DOI
  74. [80]Aoki H. Ohnishi H. Hama K. Ishijima T. Satoh Y. Hanatsuka K. Ohashi A. Wada S. Miyata T. Kita H. Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK-dependent pathways in rat pancreatic stellate cells Am. J. Physiol. Cell Physiol. 2006 290 C1100 C1108 10.1152/ajpcell.00465.2005 16371439 · DOI
  75. [82]Zhang A. Qian Y. Ye Z. Chen H. Xie H. Zhou L. Shen Y. Zheng S. Cancer-associated fibroblasts promote M2 polarization of macrophages in pancreatic ductal adenocarcinoma Cancer Med. 2017 6 463 470 10.1002/cam4.993 28097809 PMC5313646 · DOI
  76. [83]Andersson P. Yang Y. Hosaka K. Zhang Y. Fischer C. Braun H. Liu S. Yu G. Liu S. Beyaert R. Molecular mechanisms of IL-33-mediated stromal interactions in cancer metastasis JCI Insight 2018 3 10.1172/jci.insight.122375 30333314 PMC6237443 · DOI
  77. [84]Shi C. Washington M.K. Chaturvedi R. Drosos Y. Revetta F.L. Weaver C.J. Buzhardt E. Yull F.E. Blackwell T.S. Sosa-Pineda B. Fibrogenesis in pancreatic cancer is a dynamic process regulated by macrophage-stellate cell interaction Lab. Investig. 2014 94 409 421 10.1038/labinvest.2014.10 24535260 PMC3992484 · DOI
  78. [86]Kaneda M.M. Cappello P. Nguyen A.V. Ralainirina N. Hardamon C.R. Foubert P. Schmid M.C. Sun P. Mose E. Bouvet M. Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression Cancer Discov. 2016 6 870 885 10.1158/2159-8290.CD-15-1346 27179037 PMC5091937 · DOI
  79. [87]Li N. Li Y. Li Z. Huang C. Yang Y. Lang M. Cao J. Jiang W. Xu Y. Dong J. Hypoxia Inducible Factor 1 (HIF-1) Recruits Macrophage to Activate Pancreatic Stellate Cells in Pancreatic Ductal Adenocarcinoma Int. J. Mol. Sci. 2016 17 799 10.3390/ijms17060799 PMC4926333 27271610 · DOI
  80. [88]Munn D.H. Sharma M.D. Baban B. Harding H.P. Zhang Y. Ron D. Mellor A.L. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase Immunity 2005 22 633 642 10.1016/j.immuni.2005.03.013 15894280 · DOI
  81. [89]Rodriguez P.C. Quiceno D.G. Ochoa A.C. L-arginine availability regulates T-lymphocyte cell-cycle progression Blood 2007 109 1568 1573 10.1182/blood-2006-06-031856 17023580 PMC1794048 · DOI · Paper page
  82. [90]Rodriguez P.C. Zea A.H. DeSalvo J. Culotta K.S. Zabaleta J. Quiceno D.G. Ochoa J.B. Ochoa A.C. L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes J. Immunol. 2003 171 1232 1239 10.4049/jimmunol.171.3.1232 12874210 · DOI
  83. [91]Rodriguez P.C. Quiceno D.G. Zabaleta J. Ortiz B. Zea A.H. Piazuelo M.B. Delgado A. Correa P. Brayer J. Sotomayor E.M. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses Cancer Res. 2004 64 5839 5849 10.1158/0008-5472.CAN-04-0465 15313928 · DOI · Paper page
  84. [92]Kalinski P. Regulation of immune responses by prostaglandin E2 J. Immunol. 2012 188 21 28 10.4049/jimmunol.1101029 22187483 PMC3249979 · DOI
  85. [93]Oh S.A. Li M.O. TGF-β: Guardian of T cell function J. Immunol. 2013 191 3973 3979 10.4049/jimmunol.1301843 24098055 PMC3856438 · DOI
  86. [94]Ruffell B. Chang-Strachan D. Chan V. Rosenbusch A. Ho C.M. Pryer N. Daniel D. Hwang E.S. Rugo H.S. Coussens L.M. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells Cancer Cell 2014 26 623 637 10.1016/j.ccell.2014.09.006 25446896 PMC4254570 · DOI · Paper page
  87. [96]Sica A. Saccani A. Bottazzi B. Polentarutti N. Vecchi A. van Damme J. Mantovani A. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages J. Immunol. 2000 164 762 767 10.4049/jimmunol.164.2.762 10623821 · DOI
  88. [97]Parihar R. Dierksheide J. Hu Y. Carson W.E. IL-12 enhances the natural killer cell cytokine response to Ab-coated tumor cells J. Clin. Investig. 2002 110 983 992 10.1172/JCI0215950 12370276 PMC151155 · DOI
  89. [98]Krneta T. Gillgrass A. Poznanski S. Chew M. Lee A.J. Kolb M. Ashkar A.A. M2-polarized and tumor-associated macrophages alter NK cell phenotype and function in a contact-dependent manner J. Leukoc. Biol. 2017 101 285 295 10.1189/jlb.3A1215-552R 27493241 · DOI
  90. [99]Kuang D.M. Zhao Q. Peng C. Xu J. Zhang J.P. Wu C. Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1 J. Exp. Med. 2009 206 1327 1337 10.1084/jem.20082173 19451266 PMC2715058 · DOI
  91. [100]Ojalvo L.S. King W. Cox D. Pollard J.W. High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors Am. J. Pathol. 2009 174 1048 1064 10.2353/ajpath.2009.080676 19218341 PMC2665764 · DOI
  92. [101]Daley D. Mani V.R. Mohan N. Akkad N. Ochi A. Heindel D.W. Lee K.B. Zambirinis C.P. Pandian G.S.B. Savadkar S. Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance Nat. Med. 2017 23 556 567 10.1038/nm.4314 28394331 PMC5419876 · DOI
  93. [102]Daley D. Mani V.R. Mohan N. Akkad N. Pandian G. Savadkar S. Lee K.B. Torres-Hernandez A. Aykut B. Diskin B. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma J. Exp. Med. 2017 214 1711 1724 10.1084/jem.20161707 28442553 PMC5461004 · DOI · Paper page
  94. [103]Savage N.D. de Boer T. Walburg K.V. Joosten S.A. van Meijgaarden K. Geluk A. Ottenhoff T.H. Human anti-inflammatory macrophages induce Foxp3+ GITR+ CD25+ regulatory T cells, which suppress via membrane-bound TGFbeta-1 J. Immunol. 2008 181 2220 2226 10.4049/jimmunol.181.3.2220 18641362 · DOI
  95. [104]Büchler P. Reber H.A. Büchler M. Shrinkante S. Büchler M.W. Friess H. Semenza G.L. Hines O.J. Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer Pancreas 2003 26 56 64 10.1097/00006676-200301000-00010 12499918 · DOI
  96. [105]Shibaji T. Nagao M. Ikeda N. Kanehiro H. Hisanaga M. Ko S. Fukumoto A. Nakajima Y. Prognostic significance of HIF-1 alpha overexpression in human pancreatic cancer Anticancer Res. 2003 23 4721 4727 14981919
  97. [106]Itakura J. Ishiwata T. Friess H. Fujii H. Matsumoto Y. Büchler M.W. Korc M. Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression Clin. Cancer Res. 1997 3 1309 1316 9815813
  98. [108]Yang Y. Guo Z. Chen W. Wang X. Cao M. Han X. Zhang K. Teng B. Cao J. Wu W. M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2 Mol. Ther. 2021 29 1226 1238 10.1016/j.ymthe.2020.11.024 33221435 PMC7934635 · DOI
  99. [109]Huang C. Li Z. Li N. Li Y. Chang A. Zhao T. Wang X. Wang H. Gao S. Yang S. Interleukin 35 Expression Correlates With Microvessel Density in Pancreatic Ductal Adenocarcinoma, Recruits Monocytes, and Promotes Growth and Angiogenesis of Xenograft Tumors in Mice Gastroenterology 2018 154 675 688 10.1053/j.gastro.2017.09.039 28989066 · DOI
  100. [110]Atanasov G. Pötner C. Aust G. Schierle K. Dietel C. Benzing C. Krenzien F. Bartels M. Eichfeld U. Schmelzle M. TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas Oncotarget 2018 9 29715 29726 10.18632/oncotarget.25690 30038715 PMC6049857 · DOI
  101. [112]Venneri M.A. De Palma M. Ponzoni M. Pucci F. Scielzo C. Zonari E. Mazzieri R. Doglioni C. Naldini L. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer Blood 2007 109 5276 5285 10.1182/blood-2006-10-053504 17327411 · DOI
  102. [113]Kurahara H. Takao S. Shinchi H. Maemura K. Mataki Y. Sakoda M. Hayashi T. Kuwahata T. Minami K. Ueno S. Significance of lymphangiogenesis in primary tumor and draining lymph nodes during lymphatic metastasis of pancreatic head cancer J. Surg. Oncol. 2010 102 809 815 10.1002/jso.21744 20886557 · DOI
  103. [114]Wang Z. Wu J. Li G. Zhang X. Tong M. Wu Z. Liu Z. Lymphangiogenesis and biological behavior in pancreatic carcinoma and other pancreatic tumors Mol. Med. Rep. 2012 5 959 963 10.3892/mmr.2012.745 22246595 PMC3493034 · DOI
  104. [115]Riabov V. Gudima A. Wang N. Mickley A. Orekhov A. Kzhyshkowska J. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis Front. Physiol. 2014 5 75 10.3389/fphys.2014.00075 24634660 PMC3942647 · DOI
  105. [116]Alishekevitz D. Gingis-Velitski S. Kaidar-Person O. Gutter-Kapon L. Scherer S.D. Raviv Z. Merquiol E. Ben-Nun Y. Miller V. Rachman-Tzemah C. Macrophage-Induced Lymphangiogenesis and Metastasis following Paclitaxel Chemotherapy Is Regulated by VEGFR3 Cell Rep. 2016 17 1344 1356 10.1016/j.celrep.2016.09.083 27783948 PMC5098117 · DOI
  106. [117]Scavelli C. Vacca A. Di Pietro G. Dammacco F. Ribatti D. Crosstalk between angiogenesis and lymphangiogenesis in tumor progression Leukemia 2004 18 1054 1058 10.1038/sj.leu.2403355 15057248 · DOI
  107. [118]Coffelt S.B. Hughes R. Lewis C.E. Tumor-associated macrophages: Effectors of angiogenesis and tumor progression Biochim. Biophys. Acta 2009 1796 11 18 10.1016/j.bbcan.2009.02.004 19269310 · DOI
  108. [119]Gomes F.G. Nedel F. Alves A.M. Nör J.E. Tarquinio S.B. Tumor angiogenesis and lymphangiogenesis: Tumor/endothelial crosstalk and cellular/microenvironmental signaling mechanisms Life Sci. 2013 92 101 107 10.1016/j.lfs.2012.10.008 23178150 PMC3740377 · DOI
  109. [120]Kurahara H. Shinchi H. Mataki Y. Maemura K. Noma H. Kubo F. Sakoda M. Ueno S. Natsugoe S. Takao S. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer J. Surg. Res. 2011 167 e211 e219 10.1016/j.jss.2009.05.026 19765725 · DOI
  110. [121]Kurahara H. Takao S. Kuwahata T. Nagai T. Ding Q. Maeda K. Shinchi H. Mataki Y. Maemura K. Matsuyama T. Clinical significance of folate receptor β-expressing tumor-associated macrophages in pancreatic cancer Ann. Surg. Oncol. 2012 19 2264 2271 10.1245/s10434-012-2263-0 22350599 · DOI
  111. [122]Quail D.F. Joyce J.A. Microenvironmental regulation of tumor progression and metastasis Nat. Med. 2013 19 1423 1437 10.1038/nm.3394 24202395 PMC3954707 · DOI · Paper page
  112. [123]Yachida S. Iacobuzio-Donahue C.A. The pathology and genetics of metastatic pancreatic cancer Arch. Pathol. Lab. Med. 2009 133 413 422 10.5858/133.3.413 19260747 · DOI
  113. [124]Chen Q. Wang J. Zhang Q. Zhang J. Lou Y. Yang J. Chen Y. Wei T. Zhang J. Fu Q. Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages Br. J. Cancer 2019 121 786 795 10.1038/s41416-019-0595-2 31588122 PMC6889176 · DOI
  114. [125]Meng F. Li W. Li C. Gao Z. Guo K. Song S. CCL18 promotes epithelial-mesenchymal transition, invasion and migration of pancreatic cancer cells in pancreatic ductal adenocarcinoma Int. J. Oncol. 2015 46 1109 1120 10.3892/ijo.2014.2794 25502147 · DOI
  115. [126]Chen S.J. Lian G.D. Li J.J. Zhang Q.B. Zeng L.J. Yang K.G. Huang C.M. Li Y.Q. Chen Y.T. Huang K.H. Tumor-driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL-8 Cancer Med. 2018 7 5679 5690 10.1002/cam4.1824 30311406 PMC6246928 · DOI
  116. [127]Tekin C. Aberson H.L. Waasdorp C. Hooijer G.K.J. de Boer O.J. Dijk F. Bijlsma M.F. Spek C.A. Macrophage-secreted MMP9 induces mesenchymal transition in pancreatic cancer cells via PAR1 activation Cell. Oncol. 2020 43 1161 1174 10.1007/s13402-020-00549-x 32809114 PMC7717035 · DOI
  117. [128]Liu C.-Y. Xu J.-Y. Shi X.-Y. Huang W. Ruan T.-Y. Xie P. Ding J.-L. M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway Lab. Investig. 2013 93 844 854 10.1038/labinvest.2013.69 23752129 · DOI
  118. [129]Ye H. Zhou Q. Zheng S. Li G. Lin Q. Wei L. Fu Z. Zhang B. Liu Y. Li Z. Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma Cell Death Dis. 2018 9 453 10.1038/s41419-018-0486-0 29670110 PMC5906621 · DOI
  119. [130]Kaplan R.N. Riba R.D. Zacharoulis S. Bramley A.H. Vincent L. Costa C. MacDonald D.D. Jin D.K. Shido K. Kerns S.A. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche Nature 2005 438 820 827 10.1038/nature04186 16341007 PMC2945882 · DOI · Paper page
  120. [132]Joyce J.A. Pollard J.W. Microenvironmental regulation of metastasis Nat. Rev. Cancer 2009 9 239 252 10.1038/nrc2618 19279573 PMC3251309 · DOI · Paper page
  121. [133]Costa-Silva B. Aiello N.M. Ocean A.J. Singh S. Zhang H. Thakur B.K. Becker A. Hoshino A. Mark M.T. Molina H. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver Nat. Cell Biol. 2015 17 816 826 10.1038/ncb3169 25985394 PMC5769922 · DOI · Paper page
  122. [134]Quiñonero F. Mesas C. Doello K. Cabeza L. Perazzoli G. Jimenez-Luna C. Rama A.R. Melguizo C. Prados J. The challenge of drug resistance in pancreatic ductal adenocarcinoma: A current overview Cancer Biol. Med. 2019 16 688 699 10.20892/j.issn.2095-3941.2019.0252 31908888 PMC6936232 · DOI
  123. [135]Kuwada K. Kagawa S. Yoshida R. Sakamoto S. Ito A. Watanabe M. Ieda T. Kuroda S. Kikuchi S. Tazawa H. The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer J. Exp. Clin. Cancer Res. 2018 37 307 10.1186/s13046-018-0981-2 30537992 PMC6288926 · DOI
  124. [136]Weizman N. Krelin Y. Shabtay-Orbach A. Amit M. Binenbaum Y. Wong R.J. Gil Z. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase Oncogene 2014 33 3812 3819 10.1038/onc.2013.357 23995783 · DOI · Paper page
  125. [137]Buchholz S.M. Goetze R.G. Singh S.K. Ammer-Herrmenau C. Richards F.M. Jodrell D.I. Buchholz M. Michl P. Ellenrieder V. Hessmann E. Depletion of Macrophages Improves Therapeutic Response to Gemcitabine in Murine Pancreas Cancer Cancers 2020 12 1978 10.3390/cancers12071978 PMC7409345 32698524 · DOI
  126. [138]Ireland L. Santos A. Ahmed M.S. Rainer C. Nielsen S.R. Quaranta V. Weyer-Czernilofsky U. Engle D.D. Perez-Mancera P.A. Coupland S.E. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors Cancer Res. 2016 76 6851 6863 10.1158/0008-5472.CAN-16-1201 27742686 PMC5321488 · DOI
  127. [139]Zhang M. Yan L. Wang G.J. Jin R. Resistin effects on pancreatic cancer progression and chemoresistance are mediated through its receptors CAP1 and TLR4 J. Cell. Physiol. 2019 234 9457 9466 10.1002/jcp.27631 30317640 · DOI
  128. [140]Michaels A.D. Newhook T.E. Adair S.J. Morioka S. Goudreau B.J. Nagdas S. Mullen M.G. Persily J.B. Bullock T.N.J. Slingluff C.L. Jr. CD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer Cli. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2018 24 1415 1425 10.1158/1078-0432.CCR-17-2283 29288236 PMC6296745 · DOI
  129. [141]Germano G. Frapolli R. Belgiovine C. Anselmo A. Pesce S. Liguori M. Erba E. Uboldi S. Zucchetti M. Pasqualini F. Role of macrophage targeting in the antitumor activity of trabectedin Cancer Cell 2013 23 249 262 10.1016/j.ccr.2013.01.008 23410977 · DOI
  130. [142]Borgoni S. Iannello A. Cutrupi S. Allavena P. D’Incalci M. Novelli F. Cappello P. Depletion of tumor-associated macrophages switches the epigenetic profile of pancreatic cancer infiltrating T cells and restores their anti-tumor phenotype Oncoimmunology 2018 7 e1393596 10.1080/2162402X.2017.1393596 29308326 PMC5749621 · DOI
  131. [143]Céspedes M.V. Guillén M.J. López-Casas P.P. Sarno F. Gallardo A. Álamo P. Cuevas C. Hidalgo M. Galmarini C.M. Allavena P. Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models Dis. Models Mech. 2016 9 1461 1471 10.1242/dmm.026369 PMC5200894 27780828 · DOI
  132. [144]Stanley E.R. Chitu V. CSF-1 receptor signaling in myeloid cells Cold Spring Harb. Perspect. Biol. 2014 6 a021857 10.1101/cshperspect.a021857 24890514 PMC4031967 · DOI · Paper page
  133. [146]Zhu Y. Knolhoff B.L. Meyer M.A. Nywening T.M. West B.L. Luo J. Wang-Gillam A. Goedegebuure S.P. Linehan D.C. DeNardo D.G. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models Cancer Res. 2014 74 5057 5069 10.1158/0008-5472.CAN-13-3723 25082815 PMC4182950 · DOI · Paper page
  134. [147]Jones K.I. Tiersma J. Yuzhalin A.E. Gordon-Weeks A.N. Buzzelli J. Im J.H. Muschel R.J. Radiation combined with macrophage depletion promotes adaptive immunity and potentiates checkpoint blockade EMBO Mol. Med. 2018 10 10.15252/emmm.201809342 PMC6284388 30442705 · DOI
  135. [148]Saung M.T. Muth S. Ding D. Thomas D.L. 2nd Blair A.B. Tsujikawa T. Coussens L. Jaffee E.M. Zheng L. Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer J. Immunother. Cancer 2018 6 118 10.1186/s40425-018-0435-6 30424804 PMC6234697 · DOI
  136. [149]Nywening T.M. Wang-Gillam A. Sanford D.E. Belt B.A. Panni R.Z. Cusworth B.M. Toriola A.T. Nieman R.K. Worley L.A. Yano M. 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. 2016 17 651 662 10.1016/S1470-2045(16)00078-4 27055731 PMC5407285 · DOI
  137. [150]Linehan D. Noel M.S. Hezel A.F. Wang-Gillam A. Eskens F. Sleijfer S. Desar I.M.E. Erdkamp F. Wilmink J. Diehl J. Overall survival in a trial of orally administered CCR2 inhibitor CCX872 in locally advanced/metastatic pancreatic cancer: Correlation with blood monocyte counts J. Clin. Oncol. 2018 36 92 10.1200/JCO.2018.36.5_suppl.92 · DOI
  138. [151]Kaneda M.M. Messer K.S. Ralainirina N. Li H. Leem C.J. Gorjestani S. Woo G. Nguyen A.V. Figueiredo C.C. Foubert P. PI3Kγ is a molecular switch that controls immune suppression Nature 2016 539 437 442 10.1038/nature19834 27642729 PMC5479689 · DOI
  139. [153]Gunderson A.J. Kaneda M.M. Tsujikawa T. Nguyen A.V. Affara N.I. Ruffell B. Gorjestani S. Liudahl S.M. Truitt M. Olson P. Bruton Tyrosine Kinase-Dependent Immune Cell Cross-talk Drives Pancreas Cancer Cancer Discov. 2016 6 270 285 10.1158/2159-8290.CD-15-0827 26715645 PMC4783268 · DOI
  140. [154]Ueta T. Ishihara K. Notomi S. Lee J.-J. Maidana D.E. Efstathiou N.E. Murakami Y. Hasegawa E. Azuma K. Toyono T. RIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization Proc. Natl. Acad. Sci. USA 2019 116 23705 10.1073/pnas.1908355116 31685620 PMC6876205 · DOI
  141. [155]Wang W. Marinis J.M. Beal A.M. Savadkar S. Wu Y. Khan M. Taunk P.S. Wu N. Su W. Wu J. RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer Cancer Cell 2018 34 757 774 10.1016/j.ccell.2018.10.006 30423296 PMC6836726 · DOI
  142. [156]Bennett S.R. Carbone F.R. Karamalis F. Flavell R.A. Miller J.F. Heath W.R. Help for cytotoxic-T-cell responses is mediated by CD40 signalling Nature 1998 393 478 480 10.1038/30996 9624004 · DOI
  143. [157]Hernandez M.G. Shen L. Rock K.L. CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell help J. Immunol. 2008 180 4382 4390 10.4049/jimmunol.180.7.4382 18354158 · DOI
  144. [158]Beatty G.L. Chiorean E.G. Fishman M.P. Saboury B. Teitelbaum U.R. Sun W. Huhn R.D. Song W. Li D. Sharp L.L. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans Science 2011 331 1612 1616 10.1126/science.1198443 21436454 PMC3406187 · DOI
  145. [160]Stromnes I.M. Burrack A.L. Hulbert A. Bonson P. Black C. Brockenbrough J.S. Raynor J.F. Spartz E.J. Pierce R.H. Greenberg P.D. Differential Effects of Depleting versus Programming Tumor-Associated Macrophages on Engineered T Cells in Pancreatic Ductal Adenocarcinoma Cancer Immunol. Res. 2019 7 977 989 10.1158/2326-6066.CIR-18-0448 31028033 PMC6548612 · DOI
  146. [161]Ma H.S. Poudel B. Torres E.R. Sidhom J.W. Robinson T.M. Christmas B. Scott B. Cruz K. Woolman S. Wall V.Z. A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity Cancer Immunol. Res. 2019 7 428 442 10.1158/2326-6066.CIR-18-0061 30642833 PMC6397686 · DOI
  147. [163]Gahmberg C.G. Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules Curr. Opin. Cell Biol. 1997 9 643 650 10.1016/S0955-0674(97)80117-2 9330867 · DOI
  148. [164]Sica A. Mantovani A. Macrophage plasticity and polarization: In vivo veritas J. Clin. Investig. 2012 122 787 795 10.1172/JCI59643 22378047 PMC3287223 · DOI · Paper page
  149. [165]Maiguel D. Faridi M.H. Wei C. Kuwano Y. Balla K.M. Hernandez D. Barth C.J. Lugo G. Donnelly M. Nayer A. Small molecule-mediated activation of the integrin CD11b/CD18 reduces inflammatory disease Sci. Signal. 2011 4 ra57 10.1126/scisignal.2001811 21900205 PMC4507414 · DOI
  150. [166]Panni R.Z. Herndon J.M. Zuo C. Hegde S. Hogg G.D. Knolhoff B.L. Breden M.A. Li X. Krisnawan V.E. Khan S.Q. Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies Sci. Transl. Med. 2019 11 10.1126/scitranslmed.aau9240 31270275 PMC7197026 · DOI
  151. [167]Jaiswal S. Jamieson C.H. Pang W.W. Park C.Y. Chao M.P. Majeti R. Traver D. van Rooijen N. Weissman I.L. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis Cell 2009 138 271 285 10.1016/j.cell.2009.05.046 19632178 PMC2775564 · DOI
  152. [168]Sick E. Jeanne A. Schneider C. Dedieu S. Takeda K. Martiny L. CD47 update: A multifaceted actor in the tumour microenvironment of potential therapeutic interest Br. J. Pharmacol. 2012 167 1415 1430 10.1111/j.1476-5381.2012.02099.x 22774848 PMC3514757 · DOI
  153. [169]Cioffi M. Trabulo S. Hidalgo M. Costello E. Greenhalf W. Erkan M. Kleeff J. Sainz B. Jr. Heeschen C. Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms Clin. Cancer Res. 2015 21 2325 2337 10.1158/1078-0432.CCR-14-1399 25717063 · DOI
  154. [170]Kamerkar S. LeBleu V.S. Sugimoto H. Yang S. Ruivo C.F. Melo S.A. Lee J.J. Kalluri R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer Nature 2017 546 498 503 10.1038/nature22341 28607485 PMC5538883 · DOI · Paper page
  155. [171]Pan Y. Lu F. Fei Q. Yu X. Xiong P. Yu X. Dang Y. Hou Z. Lin W. Lin X. Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer J. Hematol. Oncol. 2019 12 124 10.1186/s13045-019-0822-6 31771616 PMC6880569 · DOI
  156. [172]Xi Q. Chen Y. Yang G.Z. Zhang J.Y. Zhang L.J. Guo X.D. Zhao J.Y. Xue Z.Y. Li Y. Zhang R. miR-128 Regulates Tumor Cell CD47 Expression and Promotes Anti-tumor Immunity in Pancreatic Cancer Front. Immunol. 2020 11 890 10.3389/fimmu.2020.00890 32536914 PMC7267029 · DOI
  157. [173]Xi Q. Zhang J. Yang G. Zhang L. Chen Y. Wang C. Zhang Z. Guo X. Zhao J. Xue Z. Restoration of miR-340 controls pancreatic cancer cell CD47 expression to promote macrophage phagocytosis and enhance antitumor immunity J. Immunother. Cancer 2020 8 e000253 10.1136/jitc-2019-000253 32503944 PMC7279671 · DOI · Paper page
  158. [174]El Chartouni C. Schwarzfischer L. Rehli M. Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming Immunobiology 2010 215 821 825 10.1016/j.imbio.2010.05.031 20580461 · DOI
  159. [176]Satoh T. Takeuchi O. Vandenbon A. Yasuda K. Tanaka Y. Kumagai Y. Miyake T. Matsushita K. Okazaki T. Saitoh T. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection Nat. Immunol. 2010 11 936 944 10.1038/ni.1920 20729857 · DOI · Paper page
  160. [177]Bastea L.I. Liou G.-Y. Pandey V. Fleming A.K. von Roemeling C.A. Doeppler H. Li Z. Qiu Y. Edenfield B. Copland J.A. Pomalidomide Alters Pancreatic Macrophage Populations to Generate an Immune-Responsive Environment at Precancerous and Cancerous Lesions Cancer Res. 2019 79 1535 1548 10.1158/0008-5472.CAN-18-1153 30696657 PMC6445670 · DOI
  161. [178]Shirai Y. Saito N. Uwagawa T. Shiba H. Horiuchi T. Iwase R. Haruki K. Ohashi T. Yanaga K. Pomalidomide promotes chemosensitization of pancreatic cancer by inhibition of NF-κB Oncotarget 2018 9 15292 15301 10.18632/oncotarget.24577 29632644 PMC5880604 · DOI
  162. [179]De Palma M. Venneri M.A. Galli R. Sergi Sergi L. Politi L.S. Sampaolesi M. Naldini L. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors Cancer Cell 2005 8 211 226 10.1016/j.ccr.2005.08.002 16169466 · DOI · Paper page
  163. [180]Harney A.S. Karagiannis G.S. Pignatelli J. Smith B.D. Kadioglu E. Wise S.C. Hood M.M. Kaufman M.D. Leary C.B. Lu W.P. The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2(Hi) Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors Mol. Cancer Ther. 2017 16 2486 2501 10.1158/1535-7163.MCT-17-0241 28838996 PMC5669998 · DOI
  164. [181]Ho W.J. Jaffee E.M. Zheng L. The tumour microenvironment in pancreatic cancer—Clinical challenges and opportunities Nat. Rev. Clin. Oncol. 2020 17 527 540 10.1038/s41571-020-0363-5 32398706 PMC7442729 · DOI
  165. [182]Mestas J. Hughes C.C. Of mice and not men: Differences between mouse and human immunology J. Immunol. 2004 172 2731 2738 10.4049/jimmunol.172.5.2731 14978070 · DOI · Paper page
  166. [183]Austyn J.M. Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage Eur. J. Immunol. 1981 11 805 815 10.1002/eji.1830111013 7308288 · DOI
  167. [184]Ruffell B. Coussens L.M. Macrophages and therapeutic resistance in cancer Cancer Cell 2015 27 462 472 10.1016/j.ccell.2015.02.015 25858805 PMC4400235 · DOI · Paper page
  168. [185]Hart P.H. Bonder C.S. Balogh J. Dickensheets H.L. Donnelly R.P. Finlay-Jones J.J. Differential responses of human monocytes and macrophages to IL-4 and IL-13 J. Leukoc. Biol. 1999 66 575 578 10.1002/jlb.66.4.575 10534111 · DOI
  169. [186]Whatcott C.J. Diep C.H. Jiang P. Watanabe A. LoBello J. Sima C. Hostetter G. Shepard H.M. Von Hoff D.D. Han H. Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer Clin. Cancer Res. 2015 21 3561 3568 10.1158/1078-0432.CCR-14-1051 25695692 PMC4526394 · DOI
  170. [187]Ligorio M. Sil S. Malagon-Lopez J. Nieman L.T. Misale S. Di Pilato M. Ebright R.Y. Karabacak M.N. Kulkarni A.S. Liu A. Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer Cell 2019 178 160 175.e127 10.1016/j.cell.2019.05.012 31155233 PMC6697165 · DOI
  171. [188]Machiels J.P. Gomez-Roca C. Michot J.M. Zamarin D. Mitchell T. Catala G. Eberst L. Jacob W. Jegg A.M. Cannarile M.A. Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients J. Immunother. Cancer 2020 8 e001153 10.1136/jitc-2020-001153 33097612 PMC7590375 · DOI
  172. [189]Papadopoulos K.P. Gluck L. Martin L.P. Olszanski A.J. Tolcher A.W. Ngarmchamnanrith G. Rasmussen E. Amore B.M. Nagorsen D. Hill J.S. First-in-Human Study of AMG 820, a Monoclonal Anti-Colony-Stimulating Factor 1 Receptor Antibody, in Patients with Advanced Solid Tumors Clin.Cancer Res. 2017 23 5703 10.1158/1078-0432.CCR-16-3261 28655795 · DOI
  173. [190]Soares K.C. Foley K. Olino K. Leubner A. Mayo S.C. Jain A. Jaffee E. Schulick R.D. Yoshimura K. Edil B. A preclinical murine model of hepatic metastases J. Vis. Exp. 2014 51677 10.3791/51677 25285458 PMC4378377 · DOI
  174. [191]Wu K. Lin K. Li X. Yuan X. Xu P. Ni P. Xu D. Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment Front. Immunol. 2020 11 1731 10.3389/fimmu.2020.01731 32849616 PMC7417513 · DOI
  175. [192]Collisson E.A. Sadanandam A. Olson P. Gibb W.J. Truitt M. Gu S. Cooc J. Weinkle J. Kim G.E. Jakkula L. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy Nat. Med. 2011 17 500 503 10.1038/nm.2344 21460848 PMC3755490 · DOI · Paper page
  176. [195]Zhao L. Zhao H. Yan H. Gene expression profiling of 1200 pancreatic ductal adenocarcinoma reveals novel subtypes BMC Cancer 2018 18 603 10.1186/s12885-018-4546-8 29843660 PMC5975421 · DOI
  177. [196]Lomberk G. Blum Y. Nicolle R. Nair A. Gaonkar K.S. Marisa L. Mathison A. Sun Z. Yan H. Elarouci N. Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes Nat. Commun. 2018 9 1978 10.1038/s41467-018-04383-6 29773832 PMC5958058 · DOI
  178. [198]Dijk F. Veenstra V.L. Soer E.C. Dings M.P.G. Zhao L. Halfwerk J.B. Hooijer G.K. Damhofer H. Marzano M. Steins A. Unsupervised class discovery in pancreatic ductal adenocarcinoma reveals cell-intrinsic mesenchymal features and high concordance between existing classification systems Sci. Rep. 2020 10 337 10.1038/s41598-019-56826-9 31941932 PMC6962149 · DOI
  179. [200]Juiz N. Elkaoutari A. Bigonnet M. Gayet O. Roques J. Nicolle R. Iovanna J. Dusetti N. Basal-like and classical cells coexist in pancreatic cancer revealed by single-cell analysis on biopsy-derived pancreatic cancer organoids from the classical subtype FASEB J. 2020 34 12214 12228 10.1096/fj.202000363RR 32686876 · DOI
  180. [201]Bilzer M. Roggel F. Gerbes A.L. Role of Kupffer cells in host defense and liver disease Liver Int. 2006 26 1175 1186 10.1111/j.1478-3231.2006.01342.x 17105582 · DOI
  181. [202]Wright J.R. Clearance and recycling of pulmonary surfactant Am. J. Physiol. 1990 259 L1 L12 10.1152/ajplung.1990.259.2.L1 2200279 · DOI
  182. [203]Purnama C. Ng S.L. Tetlak P. Setiagani Y.A. Kandasamy M. Baalasubramanian S. Karjalainen K. Ruedl C. Transient ablation of alveolar macrophages leads to massive pathology of influenza infection without affecting cellular adaptive immunity Eur. J. Immunol. 2014 44 2003 2012 10.1002/eji.201344359 24687623 · DOI
  183. [204]Lee B. Qiao L. Kinney B. Feng G.S. Shao J. Macrophage depletion disrupts immune balance and energy homeostasis PLoS ONE 2014 9 e99575 10.1371/journal.pone.0099575 24911652 PMC4049836 · DOI
  184. [205]Kumar V. Donthireddy L. Marvel D. Condamine T. Wang F. Lavilla-Alonso S. Hashimoto A. Vonteddu P. Behera R. Goins M.A. Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors Cancer Cell 2017 32 654 668.e655 10.1016/j.ccell.2017.10.005 29136508 PMC5827952 · DOI · Paper page
  185. [206]Li M. Li M. Yang Y. Liu Y. Xie H. Yu Q. Tian L. Tang X. Ren K. Li J. Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy J. Control Release 2020 321 23 35 10.1016/j.jconrel.2020.02.011 32035193 · DOI
  186. [207]Yang Y. Guo J. Huang L. Tackling TAMs for Cancer Immunotherapy: It’s Nano Time Trends Pharmacol. Sci. 2020 41 701 714 10.1016/j.tips.2020.08.003 32946772 PMC7652091 · DOI
  187. [208]Babicky M.L. Harper M.M. Chakedis J. Cazes A. Mose E.S. Jaquish D.V. French R.P. Childers B. Alakus H. Schmid M.C. MST1R kinase accelerates pancreatic cancer progression via effects on both epithelial cells and macrophages Oncogene 2019 38 5599 5611 10.1038/s41388-019-0811-9 30967626 PMC6625868 · DOI
  188. [209]Yao L. Wang M. Niu Z. Liu Q. Gao X. Zhou L. Liao Q. Zhao Y. Interleukin-27 inhibits malignant behaviors of pancreatic cancer cells by targeting M2 polarized tumor associated macrophages Cytokine 2017 89 194 200 10.1016/j.cyto.2015.12.003 26868086 · DOI
  189. [210]Cassier P.A. Garin G. Eberst L. Delord J.-P. Chabaud S. Terret C. Montane L. Bidaux A.-S. Laurent S. Jaubert L. MEDIPLEX: A phase 1 study of durvalumab (D) combined with pexidartinib (P) in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) J. Clin. Oncol. 2019 37 2579 10.1200/JCO.2019.37.15_suppl.2579 · DOI
  190. [211]Harb W.A. Johnson M.L. Goldman J.W. Weise A.M. Call J.A. Dudek A.Z. Gonzalez R. Cowey C.L. Eves P.T. Gollerkeri A. A phase 1b/2 study of ARRY-382, an oral inhibitor of colony stimulating factor 1 receptor (CSF1R), in combination with pembrolizumab (Pembro) for the treatment of patients (Pts) with advanced solid tumors J. Clin. Oncol. 2017 35 TPS3110 10.1200/JCO.2017.35.15_suppl.TPS3110 · DOI
  191. [212]Melisi D. Hollebecque A. Oh D.-Y. Calvo E. Varghese A.M. Borazanci E.H. Mercade T.M. Simionato F. Park J.O. Bendell J.C. A phase Ib dose-escalation and cohort-expansion study of safety and activity of the transforming growth factor (TGF) β receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer J. Clin. Oncol. 2019 37 4124 10.1200/JCO.2019.37.15_suppl.4124 · DOI
  192. [213]Chiorean E.G. Hochster H.S. Nanda S. Thornton D. Klise S. A phase II study of abemaciclib as a monotherapy and in combination with other agents in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) J. Clin. Oncol. 2017 35 TPS4150 10.1200/JCO.2017.35.15_suppl.TPS4150 · DOI
  193. [214]Tempero M. Oh D.Y. Tabernero J. Reni M. Van Cutsem E. Hendifar A. Waldschmidt D.T. Starling N. Bachet J.B. Chang H.M. Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: Phase III RESOLVE study Ann. Oncol. 2021 10.1016/j.annonc.2021.01.070 33539945 · DOI
  194. [215]Wang-Gillam A. O’Reilly E.M. Bendell J.C. Wainberg Z.A. Borazanci E.H. Bahary N. O’Hara M.H. Beatty G.L. Pant S. Cohen D.J. A randomized phase II study of cabiralizumab (cabira) + nivolumab (nivo) ± chemotherapy (chemo) in advanced pancreatic ductal adenocarcinoma (PDAC) J. Clin. Oncol. 2019 37 TPS465 10.1200/JCO.2019.37.4_suppl.TPS465 · DOI
  195. [216]Calvo A. Joensuu H. Sebastian M. Naing A. Bang Y.-J. Martin M. Roda D. Hodi F.S. Veloso A. Mataraza J. Phase Ib/II study of lacnotuzumab (MCS110) combined with spartalizumab (PDR001) in patients (pts) with advanced tumors J. Clin. Oncol. 2018 36 3014 10.1200/JCO.2018.36.15_suppl.3014 · DOI
  196. [217]Cohen D.J. Medina B. Du K.L. Coveler A.L. Manji G.A. Oberstein P.E. Perna S.K. Miller G. Phase II multi-institutional study of nivolumab (Nivo), cabiralizumab (Cabira), and stereotactic body radiotherapy (SBRT) for locally advanced unresectable pancreatic cancer (LAUPC) J. Clin. Oncol. 2019 37 TPS4163 10.1200/JCO.2019.37.15_suppl.TPS4163 · DOI
  197. [218]Coveler A.L. Bajor D.L. Masood A. Yilmaz E. Shields A.F. Javle M.M. Paluri R.K. Vaccaro G.M. Zalupski M. Grilley-Olson J.E. Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) J. Clin. Oncol. 2020 38 TPS4671 10.1200/JCO.2020.38.15_suppl.TPS4671 · DOI

Authors
Poh, A. R., & Ernst, M.
Affiliations
La Trobe University (AU)
Corresponding author
Poh, Ashleigh R.
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2021-06-08
Volume
13
Issue
12
Pages
2860
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers13122860
PMC
PMC8226457
OpenAlex
W3169917196
Cited by
106
References
223
Citations by year
2026: 21 · 2025: 21 · 2024: 26 · 2023: 25 · 2022: 10 · 2021: 3
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • La Trobe University (cc-by)
Funders
  • National Health and Medical Research Council (1025239, 1079257, 1081373, 1092788, 1166447)
  • Jack Brockhoff Foundation (JBF4656-2019)
  • Tour De Cure (-)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
pancreatic ductal adenocarcinoma, tumor-associated macrophages, tumor microenvironment, macrophage heterogeneity, macrophage depletion, macrophage reprogramming, desmoplasia, chronic inflammation, immunosuppression, metastasis, drug resistance, clinical translation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review