Natural killer cells as helper cells in dendritic cell cancer vaccines

Frontiers in Immunology

Volumn 6, Issue JAN, 2015, Pages

  Pampena, María Betina ^a   Levy, Estrella Mariel ^a  

^a Instituto Médico Especializado Alexander Fleming   (Argentina)

Author keywords

Cancer vaccines; Dendritic cells vaccines; Immunomonitoring; Natural killer cells; NK cells dendritic cells crosstalk

Indexed keywords

CANCER VACCINE; CD56 ANTIGEN; CD57 ANTIGEN; CETUXIMAB; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 15; INTERLEUKIN 2; RITUXIMAB; TRASTUZUMAB; TUMOR NECROSIS FACTOR ALPHA;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; CANCER CONTROL; CANCER IMMUNOTHERAPY; CELL MIGRATION; CELLULAR DISTRIBUTION; CYTOTOXIC LYMPHOCYTE; DENDRITIC CELL; FLOW CYTOMETRY; HUMAN; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; NATURAL KILLER CELL; NEOPLASM; NONHUMAN; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SHORT SURVEY; TUMOR MICROENVIRONMENT;

EID: 84926669281     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00013     Document Type: Short Survey

References (83)

1. Caligiuri MA. Human natural killer cells. Blood (2008) 112(3):461-9. doi:10.1182/blood-2007-09-077438
2. King A, Burrows T, Loke YW. Human uterine natural killer cells. Nat Immun (1996) 15(1):41-52.
3. Luo D, Vermijlen D, Vanderkerken K, Kuppen PJ, Seynaeve C, Eddouks M, et al. Involvement of LFA-1 in hepatic NK cell (pit cell)-mediated cytolysis and apoptosis of colon carcinoma cells. J Hepatol (1999) 31(1):110-6. doi:10.1016/S0168-8278(99)80170-6
4. Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood (1990) 76(12):2421-38.
5. Trinchieri G. Biology of natural killer cells. Adv Immunol (1989) 47:187-376. doi:10.1016/S0065-2776(08)60664-1
6. Carrega P, Bonaccorsi I, Di Carlo E, Morandi B, Paul P, Rizzello V, et al. CD56 (bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph. J Immunol (2014) 192(8):3805-15. doi:10.4049/jimmunol.1301889
7. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol (2001) 22(11):633-40. doi:10.1016/S1471-4906(01)02060-9
8. Herberman RB, Djeu J, Kay HD, Ortaldo JR, Riccardi C, Bonnard GD, et al. Natural killer cells: characteristics and regulation of activity. Immunol Rev (1979) 44:43-70. doi:10.1111/j.1600-065X.1979.tb00267.x
9. Fujimiya Y, Babiuk LA, Rouse BT. Direct lymphocytotoxicity against herpes simplex virus infected cells. Can J Microbiol (1978) 24(9):1076-81. doi:10.1139/m78-177
10. Lakshmikanth T, Burke S, Hassan TA, Kimpfler S, Ursini F, Ruggeri L, et al. NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J Clin Invest (2009) 119(5):1251-63. doi:10.1172/JCI36022
11. Stagg J, Smyth MJ. NK cell-based cancer immunotherapy. Drug News Perspect (2007) 20(3):155-63. doi:10.1358/dnp.2007.20.3.1092096
12. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol (2008) 9(5):503-10. doi:10.1038/ni1582
13. Dewan MZ, Terunuma H, Takada M, Tanaka Y, Abe H, Sata T, et al. Role of natural killer cells in hormone-independent rapid tumor formation and spontaneous metastasis of breast cancer cells in vivo. Breast Cancer Res Treat (2007) 104(3):267-75. doi:10.1007/s10549-006-9416-4
14. Zhou S, Kawakami S, Higuchi Y, Yamashita F, Hashida M. The involvement of NK cell activation following intranasal administration of CpG DNA lipoplex in the prevention of pulmonary metastasis and peritoneal dissemination in mice. Clin Exp Metastasis (2012) 29(1):63-70. doi:10.1007/s10585-011-9429-1
15. Ksienzyk A, Neumann B, Nandakumar R, Finsterbusch K, Grashoff M, Zawatzky R, et al. IRF-1 expression is essential for natural killer cells to suppress metastasis. Cancer Res (2011) 71(20):6410-8. doi:10.1158/0008-5472.CAN-11-1565
16. Smyth MJ, Thia KY, Cretney E, Kelly JM, Snook MB, Forbes CA, et al. Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol (1999) 162(11):6658-62.
17. Van den Broek MF, Kägi D, Zinkernagel RM, Hengartner H. Perforin dependence of natural killer cell-mediated tumor control in vivo. Eur J Immunol (1995) 25(12):3514-6. doi:10.1002/eji.1830251246
18. Johnsen AC, Haux J, Steinkjer B, Nonstad U, Egeberg K, Sundan A, et al. Regulation of APO-2 ligand/trail expression in NK cells-involvement in NK cell-mediated cytotoxicity. Cytokine (1999) 11(9):664-72. doi:10.1006/cyto.1999.0489
19. Lee RK, Spielman J, Zhao DY, Olsen KJ, Podack ER. Perforin, Fas ligand, and tumor necrosis factor are the major cytotoxic molecules used by lymphokine-activated killer cells. J Immunol (1996) 157(5):1919-25.
20. Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, Perussia B. Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med (1998) 188(12):2375-80. doi:10.1084/jem.188.12.2375
21. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science (2011) 331(6013):44-9. doi:10.1126/science.1198687
22. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet (2000) 356(9244):1795-9. doi:10.1016/S0140-6736(00)03231-1
23. Coca S, Perez-Piqueras J, Martinez D, Colmenarejo A, Saez MA, Vallejo C, et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer (1997) 79(12):2320-8. doi:10.1002/(SICI)1097-0142(19970615)79:12<2320::AID-CNCR5>3.0.CO;2-P
24. Villegas FR, Coca S, Villarrubia VG, Jiménez R, Chillón MJ, Jareño J, et al. Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer (2002) 35(1):23-8. doi:10.1016/S0169-5002(01)00292-6
25. Warren RP, Stembridge AM, Gardner EJ. Deficient immune function of peripheral blood mononuclear cells from patients with Gardner syndrome. Clin Exp Immunol (1985) 60(3):525-31.
26. Markowitz JF, Aiges HW, Cunningham-Rundles S, Kahn E, Teichberg S, Fisher SE, et al. Cancer family syndrome: marker studies. Gastroenterology (1986) 91(3):581-9.
27. Jovic V, Konjevic G, Radulovic S, Jelic S, Spuzic I. Impaired perforin-dependent NK cell cytotoxicity and proliferative activity of peripheral blood T cells is associated with metastatic melanoma. Tumori (2001) 87(5):324-9.
28. Menard C, Blay JY, Borg C, Michiels S, Ghiringhelli F, Robert C, et al. Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res (2009) 69:3563-9. doi:10.1158/0008-5472.CAN-08-3807
29. Sconocchia G, Arriga R, Tornillo L, Terracciano L, Ferrone S, Spagnoli GC. Melanoma cells inhibit NK cell functions. Cancer Res (2012) 72(20):5428-9. doi:10.1158/0008-5472.CAN-12-1181
30. Halama N, Braun M, Kahlert C, Spille A, Quack C, Rahbari N, et al. Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. Clin Cancer Res (2011) 17(4):678-89. doi:10.1158/1078-0432.CCR-10-2173
31. Balsamo M, Vermi W, Parodi M, Pietra G, Manzini C, Queirolo P, et al. Melanoma cells become resistant to NK-cell-mediated killing when exposed to NK-cell numbers compatible with NK-cell infiltration in the tumor. Eur J Immunol (2012) 42(7):1833-42. doi:10.1002/eji.201142179
32. Messaoudene M, Fregni G, Fourmentraux-Neves E, Chanal J, Maubec E, Mazouz-Dorval S, et al. Mature cytotoxic CD56(bright)/CD16(+) natural killer cells can infiltrate lymph nodes adjacent to metastatic melanoma. Cancer Res (2014) 74(1):81-92. doi:10.1158/0008-5472.CAN-13-1303
33. Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, et al. Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res (2012) 72(5):1070-80. doi:10.1158/0008-5472.CAN-11-3218
34. Sconocchia G, Spagnoli GC, Del Principe D, Ferrone S, Anselmi M, Wongsena W, et al. Defective infiltration of natural killer cells in MICA/B-positive renal cell carcinoma involves beta(2)-integrin-mediated interaction. Neoplasia (2009) 11(7):662-71. doi:10.1593/neo.09296
35. Mamessier E, Sylvain A, Thibult ML, Houvenaeghel G, Jacquemier J, Castellano R, et al. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest (2011) 121(9):3609-22. doi:10.1172/JCI45816
36. McKay K, Moore PC, Smoller BR, Hiatt KM. Association between natural killer cells and regression in melanocytic lesions. Hum Pathol (2011) 42:1960-4. doi:10.1016/j.humpath.2011.02.019
37. Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Che X, Iwashige H, et al. Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer (2000) 88(3):577-83. doi:10.1002/(SICI)1097-0142(20000201)88:3<577::AID-CNCR13>3.0.CO;2-V
38. Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res (2011) 71(16):5412-22. doi:10.1158/0008-5472.CAN-10-4179
39. Tomasello E, Yessaad N, Gregoire E, Hudspeth K, Luci C, Mavilio D, et al. Mapping of NKp46(+) cells in healthy human lymphoid and non-lymphoid tissues. Front Immunol (2012) 3:344. doi:10.3389/fimmu.2012.00344
40. Accomando WP, Wiencke JK, Houseman EA, Butler RA, Zheng S, Nelson HH, et al. Decreased NK cells in patients with head and neck cancer determined in archival DNA. Clin Cancer Res (2012) 18(22):6147-54. doi:10.1158/1078-0432.CCR-12-1008
41. Rocca YS, Roberti MP, Arriaga JM, Amat M, Bruno L, Pampena MB, et al. Altered phenotype in peripheral blood and tumor-associated NK cells from colorectal cancer patients. Innate Immun (2013) 19(1):76-85. doi:10.1177/1753425912453187
42. Roberti MP, Rocca YS, Amat M, Pampena MB, Loza J, Coló F, et al. IL-2-or IL-15-activated NK cells enhance Cetuximab-mediated activity against triple-negative breast cancer in xenografts and in breast cancer patients. Breast Cancer Res Treat (2012) 136(3):659-71. doi:10.1007/s10549-012-2287-y
43. Albertsson PA, Basse PH, Hokland M, Goldfarb RH, Nagelkerke JF, Nannmark U, et al. NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity. Trends Immunol (2003) 24(11):603-9. doi:10.1016/j.it.2003.09.007
44. Malmberg KJ, Bryceson YT, Carlsten M, Andersson S, Björklund A, Björkström NK, et al. NK cell-mediated targeting of human cancer and possibilities for new means of immunotherapy. Cancer Immunol Immunother (2008) 57(10):1541-52. doi:10.1007/s00262-008-0492-7
45. Sutlu T, Alici E. Natural killer cell-based immunotherapy in cancer: current insights and future prospects. J Intern Med (2009) 266(2):154-81. doi:10.1111/j.1365-2796.2009.02121.x
46. Zamai L, Ponti C, Mirandola P, Gobbi G, Papa S, Galeotti L, et al. NK cells and cancer. J Immunol (2007) 178(7):4011-6. doi:10.4049/jimmunol.178.7.4011
47. Robbins SH, Bessou G, Cornillon A, Zucchini N, Rupp B, Ruzsics Z, et al. Natural killer cells promote early CD8 T cell responses against cytomegalovirus. PLoS Pathog (2007) 3(8):e123. doi:10.1371/journal.ppat.0030123
48. Krebs P, Barnes MJ, Lampe K, Whitley K, Bahjat KS, Beutler B, et al. NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responses. Blood (2009) 113(26):6593-602. doi:10.1182/blood-2009-01-201467
49. Kalinski P, Giermasz A, Nakamura Y, Basse P, Storkus WJ, Kirkwood JM, et al. Helper role of NK cells during the induction of anticancer responses by dendritic cells. Mol Immunol (2005) 42(4):535-9. doi:10.1016/j.molimm.2004.07.038
50. Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med (2002) 195(3):327-33. doi:10.1084/jem.20010938
51. Amakata Y, Fujiyama Y, Andoh A, Hodohara K, Bamba T. Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes. Clin Exp Immunol (2001) 124(2):214-22. doi:10.1046/j.1365-2249.2001.01550.x
52. Della Chiesa M, Romagnani C, Thiel A, Moretta L, Moretta A. Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses. Blood (2006) 108(12):3851-8. doi:10.1182/blood-2006-02-004028
53. Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T, et al. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci U S A (2004) 101(47):16606-11. doi:10.1073/pnas.0407522101
54. Martín-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, et al. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol (2004) 5(12):1260-5. doi:10.1038/ni1138
55. Moretta A, Marcenaro E, Sivori S, Della Chiesa M, Vitale M, Moretta L. Early liaisons between cells of the innate immune system in inflamed peripheral tissues. Trends Immunol (2005) 26(12):668-75. doi:10.1016/j.it.2005.09.008
56. Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M, et al. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med (1999) 5(4):405-11. doi:10.1038/7403
57. Piccioli D, Sbrana S, Melandri E, Valiante NM. Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med (2002) 195(3):335-41. doi:10.1084/jem.20010934
58. Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman RM, Münz C. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med (2002) 195(3):343-51. doi:10.1084/jem.20011149
59. Moretta A. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol (2002) 2(12):957-64. doi:10.1038/nri956
60. Morandi B, Mortara L, Chiossone L, Accolla RS, Mingari MC, Moretta L, et al. Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response. PLoS One (2012) 7(6):e39170. doi:10.1371/journal.pone.0039170
61. Bouwer AL, Saunderson SC, Caldwell FJ, Damani TT, Pelham SJ, Dunn AC, et al. NK cells are required for dendritic cell-based immunotherapy at the time of tumor challenge. J Immunol (2014) 192(5):2514-21. doi:10.4049/jimmunol.1202797
62. Melero I, Rouzaut A, Motz GT, Coukos G. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discov (2014) 4(5):522-6. doi:10.1158/2159-8290.CD-13-0985
63. Sun JC, Beilke JN, Lanier LL. Adaptive immune features of natural killer cells. Nature (2009) 457(7229):557-61. doi:10.1038/nature07665
64. O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH. T cell-and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol (2006) 7(5):507-16. doi:10.1038/ni1332
65. Paust S, Gill HS, Wang BZ, Flynn MP, Moseman EA, Senman B, et al. Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses. Nat Immunol (2010) 11(12):1127-35. doi:10.1038/ni.1953
66. Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM. Cytokine-induced memory-like natural killer cells. Proc Natl Acad Sci U S A (2009) 106(6):1915-9. doi:10.1073/pnas.0813192106
67. Horowitz A, Behrens RH, Okell L, Fooks AR, Riley EM. NK cells as effectors of acquired immune responses: effector CD4+ T cell-dependent activation of NK cells following vaccination. J Immunol (2010) 185(5):2808-18. doi:10.4049/jimmunol.1000844
68. Gumá M, Angulo A, Vilches C, Gómez-Lozano N, Malats N, López-Botet M. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood (2004) 104(12):3664-71. doi:10.1182/blood-2004-05-2058
69. Lopez-Vergès S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, et al. Expansion of a unique CD57+NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci U S A (2011) 108(36):14725-32. doi:10.1073/pnas.1110900108
70. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature (2011) 480(7378):480-9. doi:10.1038/nature10673
71. Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset. Blood (2001) 97(10):3146-51. doi:10.1182/blood.V97.10.3146
72. Mazzolini G, Alfaro C, Sangro B, Feijoó E, Ruiz J, Benito A, et al. Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J Clin Oncol (2005) 23(5):999-1010. doi:10.1200/JCO.2005.00.463
73. Osada T, Clay T, Hobeika A, Lyerly HK, Morse MA. NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity. Cancer Immunol Immunother (2006) 55(9):1122-31. doi:10.1007/s00262-005-0089-3
74. Di Nicola M, Zappasodi R, Carlo-Stella C, Mortarini R, Pupa SM, Magni M, et al. Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study. Blood (2009) 113(1):18-27. doi:10.1182/blood-2008-06-165654
75. Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A (2010) 107(31):13824-9. doi:10.1073/pnas.1008051107
76. Alfaro C, Perez-Gracia JL, Suarez N, Rodriguez J, Fernandez de Sanmamed M, Sangro B, et al. Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients. J Immunol (2011) 187(11):6130-42. doi:10.4049/jimmunol.1102209
77. Baek S, Kim CS, Kim SB, Kim YM, Kwon SW, Kim Y, et al. Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial. J Transl Med (2011) 9:178. doi:10.1186/1479-5876-9-178
78. Qi CJ, Ning YL, Han YS, Min HY, Ye H, Zhu YL, et al. Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer. Cancer Immunol Immunother (2012) 61(9):1415-24. doi:10.1007/s00262-011-1192-2
79. Pellegatta S, Eoli M, Frigerio S, Antozzi C, Bruzzone MG, Cantini G, et al. The natural killer cell response and tumor debulking are associated with prolonged survival in recurrent glioblastoma patients receiving dendritic cells loaded with autologous tumor lysates. Oncoimmunology (2013) 2(3):e23401. doi:10.4161/onci.23401
80. Pampena MB, Levy EM, Blanco PA, Barrio MM, Mordoh J. Immunomonitoring in a phase II/III trial of therapeutic vaccination with CSF-470 plus BCG plus GM-CSF versus IFN alfa in patients with cutaneous melanoma. Program and Proceedings of the AACR Special Conference on Tumor Immunology. Orlando, FL: American Association of Cancer Research (2014). Abstract 50.
81. Beano A, Signorino E, Evangelista A, Brusa D, Mistrangelo M, Polimeni MA, et al. Correlation between NK function and response to trastuzumab in metastatic breast cancer patients. J Transl Med (2008) 6:25. doi:10.1186/1479-5876-6-25
82. Voskens CJ, Watanabe R, Rollins S, Campana D, Hasumi K, Mann DL. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity. J Exp Clin Cancer Res (2010) 29:134. doi:10.1186/1756-9966-29-134
83. Lee SC, Srivastava RM, López-Albaitero A, Ferrone S, Ferris RL. Natural killer (NK): dendritic cell (DC) cross talk induced by therapeutic monoclonal antibody triggers tumor antigen-specific T cell immunity. Immunol Res (2011) 50(2-3):248-54. doi:10.1007/s12026-011-8231-0