Influence of interferon-alpha combined with chemo (radio) therapy on immunological parameters in pancreatic adenocarcinoma

International Journal of Molecular Sciences

Volumn 15, Issue 3, 2014, Pages 4104-4125

  Karakhanova, Svetlana ^a   Mosl, Beate ^a   Harig, Sabine ^a   von Ahn, Katharina ^a   Fritz, Jasmin ^a   Schmidt, Jan ^a   Jäger, Dirk ^a   Werner, Jens ^b   Bazhin, Alexandr V ^a,b  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

Author keywords

CapRI; Immunomonitoring; Immunotherapy; Interferon ; Panc02 orthotopic model; Pancreatic carcinoma

Indexed keywords

ALPHA INTERFERON; B7 ANTIGEN; CD69 ANTIGEN; CD86 ANTIGEN; CISPLATIN; CYTOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; FLUOROURACIL; GAMMA INTERFERON; GRANZYME B; HLA DR ANTIGEN; INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 17; TUMOR NECROSIS FACTOR ALPHA; ANTINEOPLASTIC AGENT;

ADULT; AGED; ANIMAL CELL; ANIMAL MODEL; ARTICLE; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CD4 CD8 RATIO; CELL ACTIVATION; CHEMORADIOTHERAPY; CLINICAL ARTICLE; CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; CYTOTOXICITY; ENZYME LINKED IMMUNOSPOT ASSAY; EXTERNAL BEAM RADIOTHERAPY; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; HUMAN; HUMAN CELL; IMMUNOMODULATION; LEUKOCYTE COUNT; MALE; MIDDLE AGED; MOUSE; NONHUMAN; OVERALL SURVIVAL; PANCREAS ADENOCARCINOMA; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEIN EXPRESSION; ADENOCARCINOMA; ANIMAL; BLOOD; C57BL MOUSE; CLINICAL TRIAL; FLOW CYTOMETRY; IMMUNOLOGICAL MONITORING; K562 CELL LINE; MULTICENTER STUDY; NEOPLASMS, EXPERIMENTAL; PANCREATIC NEOPLASMS; PATHOLOGY; PHASE 2 CLINICAL TRIAL; PROCEDURES; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME; TUMOR CELL LINE;

ADENOCARCINOMA; AGED; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE, TUMOR; CHEMORADIOTHERAPY; CISPLATIN; CYTOKINES; FEMALE; FLOW CYTOMETRY; FLUOROURACIL; HUMANS; INTERFERON-ALPHA; K562 CELLS; LEUKOCYTE COUNT; MALE; MICE, INBRED C57BL; MIDDLE AGED; MONITORING, IMMUNOLOGIC; NEOPLASMS, EXPERIMENTAL; PANCREATIC NEOPLASMS; TREATMENT OUTCOME;

EID: 84896445763     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms15034104     Document Type: Article

References (46)

1. Jemal, A.; Tiwari, R. C.; Murray, T.; Ghafoor, A.; Samuels, A.; Ward, E.; Feuer, E. J.; Thun, M. J. Cancer statistics, 2004. CA Cancer J. Clin. 2004, 54, 8-29.
2. Neoptolemos, J. P.; Stocken, D. D.; Friess, H.; Bassi, C.; Dunn, J. A.; Hickey, H.; Beger, H.; Fernandez-Cruz, L.; Dervenis, C.; Lacaine, F.; et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N. Engl. J. Med. 2004, 350, 1200-1210.
3. Oettle, H.; Post, S.; Neuhaus, P.; Gellert, K.; Langrehr, J.; Ridwelski, K.; Schramm, H.; Fahlke, J.; Zuelke, C.; Burkart, C.; et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: A randomized controlled trial. JAMA 2007, 297, 267-277.
4. Neoptolemos, J. P.; Stocken, D. D.; Bassi, C.; Ghaneh, P.; Cunningham, D.; Goldstein, D.; Padbury, R.; Moore, M. J.; Gallinger, S.; Mariette, C.; et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs. gemcitabine following pancreatic cancer resection: A randomized controlled trial. JAMA 2010, 304, 1073-1081.
5. Dillman, R. O. Cancer immunotherapy. Cancer Biother. Radiopharm. 2011, 26, 1-64.
6. Hodi, F. S.; O'Day, S. J.; McDermott, D. F.; Weber, R. W.; Sosman, J. A.; Haanen, J. B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J. C.; et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010, 363, 711-723.
7. Lake, R. A.; Robinson, B. W. Immunotherapy and chemotherapy-A practical partnership. Nat. Rev. Cancer 2005, 5, 397-405.
8. Knaebel, H. P.; Marten, A.; Schmidt, J.; Hoffmann, K.; Seiler, C.; Lindel, K.; Schmitz-Winnenthal, H.; Fritz, S.; Herrmann, T.; Goldschmidt, H.; et al. Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment vs. 5-FU alone for patients with resected pancreatic adenocarcinoma-Capri: Study protocol [isrctn62866759]. BMC Cancer 2005, 5, 37.
9. Atkins, M. B.; Hsu, J.; Lee, S.; Cohen, G. I.; Flaherty, L. E.; Sosman, J. A.; Sondak, V. K.; Kirkwood, J. M. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (e3695): A trial coordinated by the eastern cooperative oncology group. J. Clin. Oncol. 2008, 26, 5748-5754.
10. Garbe, C.; Radny, P.; Linse, R.; Dummer, R.; Gutzmer, R.; Ulrich, J.; Stadler, R.; Weichenthal, M.; Eigentler, T.; Ellwanger, U.; et al. Adjuvant low-dose interferon {alpha}2a with or without dacarbazine compared with surgery alone: A prospective-randomized phase III decog trial in melanoma patients with regional lymph node metastasis. Ann. Oncol. 2008, 19, 1195-1201.
11. Hauschild, A.; Weichenthal, M.; Rass, K.; Linse, R.; Ulrich, J.; Stadler, R.; Volkenandt, M.; Grabbe, S.; Proske, U.; Schadendorf, D.; et al. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma. J. Clin. Oncol. 2009, 27, 3496-3502.
12. Hudes, G.; Carducci, M.; Tomczak, P.; Dutcher, J.; Figlin, R.; Kapoor, A.; Staroslawska, E.; Sosman, J.; McDermott, D.; Bodrogi, I.; et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 2007, 356, 2271-2281.
13. Iacopino, F.; Ferrandina, G.; Scambia, G.; Benedetti-Panici, P.; Mancuso, S.; Sica, G. Interferons inhibit egf-stimulated cell growth and reduce egf binding in human breast cancer cells. Anticancer Res. 1996, 16, 1919-1924.
14. Vitale, G.; van Eijck, C. H.; van Koetsveld Ing, P. M.; Erdmann, J. I.; Speel, E. J.; van der Wansem Ing, K.; Mooij, D. M.; Colao, A.; Lombardi, G.; Croze, E.; et al. Type I interferons in the treatment of pancreatic cancer: Mechanisms of action and role of related receptors. Ann. Surg. 2007, 246, 259-268.
15. Caraglia, M.; Marra, M.; Tagliaferri, P.; Lamberts, S. W.; Zappavigna, S.; Misso, G.; Cavagnini, F.; Facchini, G.; Abbruzzese, A.; Hofland, L. J.; et al. Emerging strategies to strengthen the anti-tumour activity of type I interferons: Overcoming survival pathways. Curr. Cancer Drug Targets 2009, 9, 690-704.
16. Vitale, G.; Zappavigna, S.; Marra, M.; Dicitore, A.; Meschini, S.; Condello, M.; Arancia, G.; Castiglioni, S.; Maroni, P.; Bendinelli, P.; et al. The ppar-gamma agonist troglitazone antagonizes survival pathways induced by stat-3 in recombinant interferon-beta treated pancreatic cancer cells. Biotechnol. Adv. 2012, 30, 169-184.
17. Dicitore, A.; Caraglia, M.; Gaudenzi, G.; Manfredi, G.; Amato, B.; Mari, D.; Persani, L.; Arra, C.; Vitale, G. Type I interferon-mediated pathway interacts with peroxisome proliferator activated receptor-gamma (ppar-gamma): At the cross-road of pancreatic cancer cell proliferation. Biochim. Biophys. Acta 2013, 1845, 42-52.
18. Hoffmann, K.; Mehrle, S.; Schmidt, J.; Buchler, M. W.; Marten, A. Interferon-alpha restitutes the chemosensitivity in pancreatic cancer. Anticancer Res. 2008, 28, 1499-1507.
19. Solorzano, C. C.; Hwang, R.; Baker, C. H.; Bucana, C. D.; Pisters, P. W.; Evans, D. B.; Killion, J. J.; Fidler, I. J. Administration of optimal biological dose and schedule of interferon alpha combined with gemcitabine induces apoptosis in tumor-associated endothelial cells and reduces growth of human pancreatic carcinoma implanted orthotopically in nude mice. Clin. Cancer Res. 2003, 9, 1858-1867.
20. Pfeffer, L. M.; Dinarello, C. A.; Herberman, R. B.; Williams, B. R.; Borden, E. C.; Bordens, R.; Walter, M. R.; Nagabhushan, T. L.; Trotta, P. P.; Pestka, S. Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons. Cancer Res. 1998, 58, 2489-2499.
21. Schmidt, J.; Abel, U.; Debus, J.; Harig, S.; Hoffmann, K.; Herrmann, T.; Bartsch, D.; Klein, J.; Mansmann, U.; Jager, D.; et al. Open-label, multicenter, randomized phase iii trial of adjuvant chemoradiation plus interferon alfa-2b vs. fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. J. Clin. Oncol. 2012, 30, 4077-4083.
22. Marten, A.; Schmidt, J.; Ose, J.; Harig, S.; Abel, U.; Munter, M. W.; Jager, D.; Friess, H.; Mayerle, J.; Adler, G.; et al. A randomized multicentre phase ii trial comparing adjuvant therapy in patients with interferon alpha-2b and 5-FU alone or in combination with either external radiation treatment and cisplatin (capri) or radiation alone regarding event-free survival-Capri-2. BMC Cancer 2009, 9, 160.
23. Esposito, I.; Kleeff, J.; Bergmann, F.; Reiser, C.; Herpel, E.; Friess, H.; Schirmacher, P.; Buchler, M. W. Most pancreatic cancer resections are r1 resections. Ann. Surg. Oncol. 2008, 15, 1651-1660.
24. Corssmit, E. P.; Heijligenberg, R.; Hack, C. E.; Endert, E.; Sauerwein, H. P.; Romijn, J. A. Effects of interferon-alpha (ifn-alpha) administration on leucocytes in healthy humans. Clin. Exp. Immunol. 1997, 107, 359-363.
25. Colombatto, P.; Oliveri, F.; Leandro, G.; Baldi, M.; Capalbo, M.; Rocca, G.; Brunetto, M. R.; Bonino, F. Platelet and white blood cell counts during therapy with different types of alpha interferon in patients with chronic viral hepatitis. Investigators of the alpha interferon study group of piemonte, Italy. Ital. J. Gastroenterol. Hepatol. 1997, 29, 441-447.
26. Toccaceli, F.; Rosati, S.; Scuderi, M.; Iacomi, F.; Picconi, R.; Laghi, V. Leukocyte and platelet lowering by some interferon types during viral hepatitis treatment. Hepatogastroenterology 1998, 45, 1748-1752.
27. Bellone, G.; Novarino, A.; Vizio, B.; Brondino, G.; Addeo, A.; Prati, A.; Giacobino, A.; Campra, D.; Fronda, G. R.; Ciuffreda, L. Impact of surgery and chemotherapy on cellular immunity in pancreatic carcinoma patients in view of an integration of standard cancer treatment with immunotherapy. Int. J. Oncol. 2009, 34, 1701-1715.
28. Luft, T.; Pang, K. C.; Thomas, E.; Hertzog, P.; Hart, D. N.; Trapani, J.; Cebon, J. Type I ifns enhance the terminal differentiation of dendritic cells. J. Immunol. 1998, 161, 1947-1953.
29. Gallucci, S.; Lolkema, M.; Matzinger, P. Natural adjuvants: Endogenous activators of dendritic cells. Nat. Med. 1999, 5, 1249-1255.
30. Hervas-Stubbs, S.; Perez-Gracia, J. L.; Rouzaut, A.; Sanmamed, M. F.; Le Bon, A.; Melero, I. Direct effects of type I interferons on cells of the immune system. Clin. Cancer Res. 2011, 17, 2619-2627.
31. Zamai, L.; Ponti, C.; Mirandola, P.; Gobbi, G.; Papa, S.; Galeotti, L.; Cocco, L.; Vitale, M. NK cells and cancer. J. Immunol. 2007, 178, 4011-4016.
32. De Gast, G. C.; Klumpen, H. J.; Vyth-Dreese, F. A.; Kersten, M. J.; Verra, N. C.; Sein, J.; Batchelor, D.; Nooijen, W. J.; Schornagel, J. H. Phase I trial of combined immunotherapy with subcutaneous granulocyte macrophage colony-stimulating factor, low-dose interleukin 2, and interferon alpha in progressive metastatic melanoma and renal cell carcinoma. Clin. Cancer Res. 2000, 6, 1267-1272.
33. Naing, A.; Reuben, J. M.; Camacho, L. H.; Gao, H.; Lee, B. N.; Cohen, E. N.; Verschraegen, C.; Stephen, S.; Aaron, J.; Hong, D.; et al. Phase I dose escalation study of sodium stibogluconate (ssg), a protein tyrosine phosphatase inhibitor, combined with interferon alpha for patients with solid tumors. J. Cancer 2011, 2, 81-89.
34. Ernstoff, M. S.; Fusi, S.; Kirkwood, J. M. Parameters of interferon action: II. Immunological effects of recombinant leukocyte interferon (ifn-alpha 2) in phase I-II trials. J. Biol. Response Mod. 1983, 2, 540-547.
35. Bekisz, J.; Sato, Y.; Johnson, C.; Husain, S. R.; Puri, R. K.; Zoon, K. C. Immunomodulatory effects of interferons in malignancies. J. Interferon Cytokine Res. 2013, 33, 154-161.
36. Ng, T. H.; Britton, G. J.; Hill, E. V.; Verhagen, J.; Burton, B. R.; Wraith, D. C. Regulation of adaptive immunity; The role of interleukin-10. Front. Immunol. 2013, 4, 129.
37. Rousset, F.; Garcia, E.; Defrance, T.; Peronne, C.; Vezzio, N.; Hsu, D. H.; Kastelein, R.; Moore, K. W.; Banchereau, J. Interleukin 10 is a potent growth and differentiation factor for activated human b lymphocytes. Proc. Natl. Acad. Sci. USA 1992, 89, 1890-1893.
38. Tatsugami, K.; Eto, M.; Naito, S. Influence of immunotherapy with interferon-alpha on regulatory t cells in renal cell carcinoma patients. J. Interferon Cytokine Res. 2010, 30, 43-48.
39. Tarhini, A. A.; Butterfield, L. H.; Shuai, Y.; Gooding, W. E.; Kalinski, P.; Kirkwood, J. M. Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-ctla4 antibody and interferon-alpha or tlr-9 agonist and gm-csf with peptide vaccination. J. Immunother. 2012, 35, 702-710.
40. Shevchenko, I.; Karakhanova, S.; Soltek, S.; Link, J.; Bayry, J.; Werner, J.; Umansky, V.; Bazhin, A. V. Low-dose gemcitabine depletes regulatory T cells and improves survival in the orthotopic panc02 model of pancreatic cancer. Int. J. Cancer 2013, 133, 98-107.
41. Bazhin, A. V.; Bayry, J.; Umansky, V.; Werner, J.; Karakhanova, S. Overcoming immunosuppression as a new immunotherapeutic approach against pancreatic cancer. Oncoimmunology 2013, 2, e25736.
42. Bazhin, A. V.; Shevchenko, I.; Umansky, V.; Werner, J.; Karakhanova, S. Two immune faces of pancreatic adenocarcinoma: Possible implication for immunotherapy. Cancer Immunol. Immunother. 2014, 63, 59-65.
43. Corbett, T. H.; Roberts, B. J.; Leopold, W. R.; Peckham, J. C.; Wilkoff, L. J.; Griswold, D. P., Jr.; Schabel, F. M., Jr. Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in c57bl/6 mice. Cancer Res. 1984, 44, 717-726.
44. Schmidt, J.; Jager, D.; Hoffmann, K.; Buchler, M. W.; Marten, A. Impact of interferon-alpha in combined chemoradioimmunotherapy for pancreatic adenocarcinoma (capri): First data from the immunomonitoring. J. Immunother. 2007, 30, 108-115.
45. Yang, Y.; Karakhanova, S.; Soltek, S.; Werner, J.; Philippov, P. P.; Bazhin, A. V. In vivo immunoregulatory properties of the novel mitochondria-targeted antioxidant skq1. Mol. Immunol. 2012, 52, 19-29.
46. GraphPad Prism Software; version 5. 01; Available Online: http://graphpad. com/scientific-software/prism/(accessed on 21 February 2014).