Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer

Cancer Immunology, Immunotherapy

Volumn 64, Issue 12, 2015, Pages 1553-1563

  Delitto, Daniel ^a   Perez, Chelsey ^a   Han, Song ^a   Gonzalo, David H ^a   Pham, Kien ^a   Knowlton, Andrea E ^b   Graves, Christina L ^b   Behrns, Kevin E ^a   Moldawer, Lyle L ^a   Thomas, Ryan M ^a   Liu, Chen ^a   George, Thomas J ^a   Trevino, Jose G ^a   Wallet, Shannon M ^b   Hughes, Steven J ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF DENTISTRY   (United States)

Author keywords

CXCL10; Epithelial cell; Immuno oncology; Interferon ; Pancreatic cancer; Tumor associated stroma

Indexed keywords

CHEMOKINE RECEPTOR CXCR3; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GEMCITABINE; HLA ANTIGEN CLASS 1; HLA ANTIGEN CLASS 2; DEOXYCYTIDINE; HLA ANTIGEN; INTERFERON;

ANTIGEN PRESENTATION; ARTICLE; CANCER PROGNOSIS; CANCER RESISTANCE; CANCER SIZE; CANCER SURVIVAL; CELL STIMULATION; CELL VIABILITY; CHRONIC PANCREATITIS; CONTROLLED STUDY; CYTOKINE RESPONSE; EPITHELIUM CELL; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNE EVASION; IMMUNOHISTOCHEMISTRY; INFLAMMATORY CELL; LYMPH NODE METASTASIS; LYMPHOCYTE ACTIVATION; OVERALL SURVIVAL; PANCREAS CANCER; PANCREATIC CANCER CELL LINE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; TUMOR DIFFERENTIATION; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; ADAPTIVE IMMUNITY; ANALOGS AND DERIVATIVES; DRUG EFFECTS; DRUG RESISTANCE; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; METABOLISM; PANCREATIC NEOPLASMS; PATHOPHYSIOLOGY; PHYSIOLOGY; TUMOR CELL CULTURE; TUMOR CELL LINE;

ADAPTIVE IMMUNITY; CELL LINE, TUMOR; CHEMOKINE CXCL10; DEOXYCYTIDINE; DRUG RESISTANCE, NEOPLASM; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENE EXPRESSION REGULATION, NEOPLASTIC; HLA ANTIGENS; HUMANS; INTERFERON-GAMMA; INTERFERONS; PANCREATIC NEOPLASMS; RECEPTORS, CXCR3; TUMOR CELLS, CULTURED; TUMOR MICROENVIRONMENT;

EID: 84947019373     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-015-1760-y     Document Type: Article

References (45)

1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74:2913–2921. doi:10.1158/0008-5472.CAN-14-0155
2. Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703. doi:10.1056/NEJMoa1304369
3. Thomas AM, Santarsiero LM, Lutz ER et al (2004) Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 200:297–306. doi:10.1084/jem.20031435
4. Winograd R, Byrne KT, Evans RA et al (2015) Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol Res 3:399–411. doi:10.1158/2326-6066.CIR-14-0215
5. Le DT, Lutz E, Uram JN et al (2013) Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 36:382–389. doi:10.1097/CJI.0b013e31829fb7a2
6. Royal RE, Levy C, Turner K et al (2010) Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 33:828–833. doi:10.1097/CJI.0b013e3181eec14c
7. Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT (2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330:827–830. doi:10.1126/science.1195300
8. Laheru D, Jaffee EM (2005) Immunotherapy for pancreatic cancer—science driving clinical progress. Nat Rev Cancer 5:459–467. doi:10.1038/nrc1630
9. Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, Friess H (2012) The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol 9:454–467. doi:10.1038/nrgastro.2012.115
10. Beatty GL, Winograd R, Evans RA et al (2015) Exclusion of T cells from pancreatic carcinomas in mice is regulated by Ly6C(low) F4/80(+) extratumoral macrophages. Gastroenterology 149:201–210. doi:10.1053/j.gastro.2015.04.010
11. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH (2012) Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21:822–835. doi:10.1016/j.ccr.2012.04.025
12. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH (2007) Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 67:9518–9527. doi:10.1158/0008-5472.CAN-07-0175
13. Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9:628–638. doi:10.1038/nrm2455
14. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95:7556–7561
15. Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800. doi:10.1038/nm730
16. Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-gamma. Annu Rev Immunol 15:749–795. doi:10.1146/annurev.immunol.15.1.749
17. Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ (1999) In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia 1:50–62
18. Trevino JG, Summy JM, Gray MJ, Nilsson MB, Lesslie DP, Baker CH, Gallick GE (2005) Expression and activity of SRC regulate interleukin-8 expression in pancreatic adenocarcinoma cells: implications for angiogenesis. Cancer Res 65:7214–7222. doi:10.1158/0008-5472.CAN-04-3858
19. Trevino JG, Verma M, Singh S et al (2013) Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic adenocarcinoma growth irrespective of gemcitabine sensitivity. Mol Cancer Ther 12:2722–2734. doi:10.1158/1535-7163.MCT-12-0719
20. Delitto D, Pham K, Vlada AC et al (2015) Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements. Am J Pathol 185:1297–1303. doi:10.1016/j.ajpath.2015.01.016
21. Bachem MG, Schneider E, Gross H et al (1998) Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology 115:421–432
22. Meng H, Lee Y, Ba Z, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ (2015) In vitro production of IL-6 and IFN-gamma is influenced by dietary variables and predicts upper respiratory tract infection incidence and severity respectively in young adults. Front Immunol 6:94. doi:10.3389/fimmu.2015.00094
23. Li X, Rendon JL, Akhtar S, Choudhry MA (2012) Activation of toll-like receptor 2 prevents suppression of T-cell interferon gamma production by modulating p38/extracellular signal-regulated kinase pathways following alcohol and burn injury. Mol Med 18:982–991. doi:10.2119/molmed.2011.00513
24. Verhoef CM, Van Roon JA, Vianen ME, Glaudemans CA, Lafeber FP, Bijlsma JW (1999) Lymphocyte stimulation by CD3-CD28 enables detection of low T cell interferon-gamma and interleukin-4 production in rheumatoid arthritis. Scand J Immunol 50:427–432
25. Arumugam T, Ramachandran V, Fournier KF et al (2009) Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res 69:5820–5828. doi:10.1158/0008-5472.CAN-08-2819
26. Trevino JG, Pillai S, Kunigal S, Singh S, Fulp WJ, Centeno BA, Chellappan SP (2012) Nicotine induces inhibitor of differentiation-1 in a Src-dependent pathway promoting metastasis and chemoresistance in pancreatic adenocarcinoma. Neoplasia 14:1102–1114
27. Romagnani P, Annunziato F, Lasagni L et al (2001) Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest 107:53–63. doi:10.1172/JCI9775
28. de Sousa Cavalcante L, Monteiro G (2014) Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 741:8–16. doi:10.1016/j.ejphar.2014.07.041
29. Kleeff J, Beckhove P, Esposito I, Herzig S, Huber PE, Lohr JM, Friess H (2007) Pancreatic cancer microenvironment. Int J Cancer 121:699–705. doi:10.1002/ijc.22871
30. Apte MV, Xu Z, Pothula S, Goldstein D, Pirola RC, Wilson JS (2015) Pancreatic cancer: the microenvironment needs attention too! Pancreatology 15:S32–S38. doi:10.1016/j.pan.2015.02.013
31. Neesse A, Algul H, Tuveson DA, Gress TM (2015) Stromal biology and therapy in pancreatic cancer: a changing paradigm. Gut 64:1476–1484. doi:10.1136/gutjnl-2015-309304
32. Lange F, Rateitschak K, Fitzner B, Pohland R, Wolkenhauer O, Jaster R (2011) Studies on mechanisms of interferon-gamma action in pancreatic cancer using a data-driven and model-based approach. Mol Cancer 10:13. doi:10.1186/1476-4598-10-13
33. Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146. doi:10.1038/nature03954
34. Bos R, Sherman LA (2010) CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res 70:8368–8377. doi:10.1158/0008-5472.CAN-10-1322
35. Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF (2004) PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 64:1140–1145
36. Feig C, Jones JO, Kraman M et al (2013) Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA 110:20212–20217. doi:10.1073/pnas.1320318110
37. Hartmann N, Giese NA, Giese T, Poschke I, Offringa R, Werner J, Ryschich E (2014) Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer. Clin Cancer Res 20:3422–3433. doi:10.1158/1078-0432.CCR-13-2972
38. Lakshmi Narendra B, Eshvendar Reddy K, Shantikumar S, Ramakrishna S (2013) Immune system: a double-edged sword in cancer. Inflamm Res 62:823–834. doi:10.1007/s00011-013-0645-9
39. Lunardi S, Jamieson NB, Lim SY et al (2014) IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival. Oncotarget 5:11064–11080
40. Chaturvedi P, Gilkes DM, Wong CC et al (2013) Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest 123:189–205. doi:10.1172/JCI64993
41. Zipin-Roitman A, Meshel T, Sagi-Assif O, Shalmon B, Avivi C, Pfeffer RM, Witz IP, Ben-Baruch A (2007) CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. Cancer Res 67:3396–3405. doi:10.1158/0008-5472.CAN-06-3087
42. Walser TC, Rifat S, Ma X et al (2006) Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res 66:7701–7707. doi:10.1158/0008-5472.CAN-06-0709
43. Kawada K, Sonoshita M, Sakashita H et al (2004) Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res 64:4010–4017. doi:10.1158/0008-5472.CAN-03-1757
44. Schober M, Jesenofsky R, Faissner R, Weidenauer C, Hagmann W, Michl P, Heuchel RL, Haas SL, Lohr JM (2014) Desmoplasia and chemoresistance in pancreatic cancer. Cancers (Basel) 6:2137–2154. doi:10.3390/cancers6042137
45. Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE (2007) Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 14:3629–3637. doi:10.1245/s10434-007-9583-5