Increased infiltration and tolerised antigen-specific CD8+ TEM cells in tumor but not peripheral blood have no impact on survival of HCMV+ glioblastoma patients

OncoImmunology

Volumn 6, Issue 8, 2017, Pages

  Bahador, M ^a   Gras Navarro, A ^a   Rahman, M A ^a   Dominguez Valentin, M ^a   Sarowar, S ^a   Ulvestad, E ^a,b   Njolstad G ^b   Lie, S A ^a   Kristoffersen, E K ^a,b   Bratland, E ^a   Chekenya, M ^a  

^a UNIVERSITY OF BERGEN   (Norway)

^b HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

Glioblastoma; HCMV; HLA restricted T cells; memory T cells; Survival

Indexed keywords

CD11B ANTIGEN; CD28 ANTIGEN; CD3 ANTIGEN; CD31 ANTIGEN; CD4 ANTIGEN; CD45RA ANTIGEN; CD45RO ANTIGEN; CD56 ANTIGEN; CD8 ANTIGEN; CHEMOKINE RECEPTOR CCR7; CYTOMEGALOVIRUS ANTIGEN PP65; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; HLA A2 ANTIGEN; L SELECTIN; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 1; PROGRAMMED DEATH 1 RECEPTOR;

AGED; ARTICLE; BIOPSY; BLOOD SAMPLING; CANCER INHIBITION; CD8+ T LYMPHOCYTE; CELL INFILTRATION; CELL SUSPENSION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DNA ISOLATION; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; FLOW CYTOMETRY; GENE SEQUENCE; GLIOBLASTOMA; HUMAN; HUMAN CYTOMEGALOVIRUS; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; IMMUNOTHERAPY; LIVE CELL IMAGING; MAJOR CLINICAL STUDY; MALE; METHYLATION; NATURAL KILLER CELL; NEOPLASM; POLYMERASE CHAIN REACTION; PREVALENCE; SURVIVAL;

EID: 85026862736     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2017.1336272     Document Type: Article

References (72)

1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007; 114:97-109; PMID:17618441; https://doi.org/10.1007/s00401-007-0243-4
2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987-96; PMID:15758009; https://doi.org/10.1056/NEJMoa043330
3. Yamashita Y, Ito Y, Isomura H, Takemura N, Okamoto A, Motomura K, Tsujiuchi T, Natsume A, Wakabayashi T, Toyokuni S, et al. Lack of presence of the human cytomegalovirus in human glioblastoma. Mod Pathol 2014; 27:922-9; PMID:24336154; https://doi.org/10.1038/modpathol.2013.219
4. Crough T, Khanna R. Immunobiology of human cytomegalovirus:From bench to bedside. Clin Microbiol Rev 2009; 22:76-98; PMID:19136435; https://doi.org/10.1128/CMR.00034-08
5. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, Nabors LB, Cobbs CG, Britt WJ. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res 2002; 62:3347-50; PMID:12067971
6. Dziurzynski K, Wei J, Qiao W, Hatiboglu MA, Kong LY, Wu A, Wang Y, Cahill D, Levine N, Prabhu S, et al. Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res 2011; 17:4642-9; PMID:21490182; https://doi.org/10.1158/1078-0432.CCR-11-0414
7. Ranganathan P, Clark PA, Kuo JS, Salamat MS, Kalejta RF. Significant association of multiple human cytomegalovirus genomic Loci with glioblastoma multiforme samples. J Virol 2012; 86:854-64; PMID:22090104; https://doi.org/10.1128/JVI.06097-11
8. Sabatier J, Uro-Coste E, Pommepuy I, Labrousse F, Allart S, Trémoulet M, Delisle MB, Brousset P. Detection of human cytomegalovirus genome and gene products in central nervous system tumours. Br J Cancer 2005; 92:747-50; PMID:15700045; https://doi.org/10.1038/sj.bjc.6602339
9. Lau SK, Chen YY, Chen WG, Diamond DJ, Mamelak AN, Zaia JA, Weiss LM. Lack of association of cytomegalovirus with human brain tumors. Mod Pathol 2005; 18:838-43; PMID:15578071; https://doi.org/10.1038/modpathol.3800352
10. Poltermann S, Schlehofer B, Steindorf K, Schnitzler P, Geletneky K, Schlehofer JR. Lack of association of herpesviruses with brain tumors. J Neurovirol 2006; 12:90-9; PMID:16798670; https://doi.org/10.1080/13550280600654573
11. Cobbs CS. Cytomegalovirus and brain tumor:Epidemiology, biology and therapeutic aspects. Curr Opin Oncol 2013; 25:682-8; PMID:24097102; https://doi.org/10.1097/CCO.0000000000000005
12. Dolan A, Cunningham C, Hector RD, Hassan-Walker AF, Lee L, Addison C, Dargan DJ, McGeoch DJ, Gatherer D, Emery VC, et al. Genetic content of wild-type human cytomegalovirus. J Gen Virol 2004; 85:1301-12; PMID:15105547; https://doi.org/10.1099/vir.0.79888-0
13. Boeckh M, Geballe AP. Cytomegalovirus:Pathogen, paradigm, and puzzle. J Clin Invest 2011; 121:1673-80; PMID:21659716; https://doi.org/10.1172/JCI45449
14. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006; 9:157-73; PMID:16530701; https://doi.org/10.1016/j.ccr.2006.02.019
15. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, et al. The somatic genomic landscape of glioblastoma. Cell 2013; 155:462-77; PMID:24120142; https://doi.org/10.1016/j.cell.2013.09.034
16. Fan QW, Cheng CK, Gustafson WC, Charron E, Zipper P, Wong RA, Chen J, Lau J, Knobbe-Thomsen C, Weller M, et al. EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma. Cancer Cell 2013; 24:438-49; PMID:24135280; https://doi.org/10.1016/j.ccr.2013.09.004
17. Joy A, Ramesh A, Smirnov I, Reiser M, Misra A, Shapiro WR, Mills GB, Kim S, Feuerstein BG. AKT pathway genes define 5 prognostic subgroups in glioblastoma. PLoS One 2014; 9:e100827; PMID:24984002; https://doi.org/10.1371/journal.pone.0100827
18. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455:1061-8; PMID:18772890; https://doi.org/10.1038/nature07385
19. Slinger E, Maussang D, Schreiber A, Siderius M, Rahbar A, Fraile-Ramos A, Lira SA, Söderberg-Nauclér C, Smit MJ. HCMV-encoded chemokine receptor US28 mediates proliferative signaling through the IL-6-STAT3 axis. Sci Signal 2010; 3:ra58; PMID:20682912; https://doi.org/10.1126/scisignal.2001180
20. Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S, Matthews K, Jones L, Crough T, Dasari V, Klein K, et al. Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 2014; 74:3466-76; PMID:24795429; https://doi.org/10.1158/0008-5472.CAN-14-0296
21. Soroceanu L, Matlaf L, Bezrookove V, Harkins L, Martinez R, Greene M, Soteropoulos P, Cobbs CS. Human cytomegalovirus US28 found in glioblastoma promotes an invasive and angiogenic phenotype. Cancer Res 2011; 71:6643-53; PMID:21900396; https://doi.org/10.1158/0008-5472.CAN-11-0744
22. Schuessler A, Walker DG, Khanna R. Cytomegalovirus as a novel target for immunotherapy of glioblastoma multiforme. Front Oncol 2014; 4:275; PMID:25340042; https://doi.org/10.3389/fonc.2014.00275
23. Soderberg-Naucler C, Rahbar A, Stragliotto G. Survival in patients with glioblastoma receiving valganciclovir. N Engl J Med 2013; 369:985-6; PMID:24004141; https://doi.org/10.1056/NEJMc1302145
24. Parry HM, Zuo J, Frumento G, Mirajkar N, Inman C, Edwards E, Griffiths M, Pratt G, Moss P. Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years. Immun Ageing 2016; 13:1; PMID:26734066; https://doi.org/10.1186/s12979-015-0056-6
25. Stowe RP, Peek MK, Cutchin MP, Goodwin JS. Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus and age. J Med Virol 2012; 84:1797-802; PMID:22997083; https://doi.org/10.1002/jmv.23397
26. Parry HM, Damery S, Hudson C, Maurer MJ, Cerhan JR, Pachnio A, Begum J, Slager SL, Fegan C, Man S, et al. Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia. Am J Hematol 2016; 91:776-81; PMID:27124884; https://doi.org/10.1002/ajh.24403
27. Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, von Zglinicki T. Inflammation, but not telomere length, predicts successful ageing at extreme old age:A longitudinal study of semi-supercentenarians. EBioMedicine 2015; 2:1549-58; PMID:26629551; https://doi.org/10.1016/j.ebiom.2015.07.029
28. Hellstrand K, Martner A, Bergstrom T. Valganciclovir in patients with glioblastoma. N Engl J Med 2013; 369:2066; PMID:24256397; https://doi.org/10.1056/NEJMc1312413
29. Rahbar A, Peredo I, Solberg NW, Taher C, Dzabic M, Xu X, Skarman P, Fornara O, Tammik C, Yaiw K, et al. Discordant humoral and cellular immune responses to Cytomegalovirus (CMV) in glioblastoma patients whose tumors are positive for CMV. Oncoimmunology 2015; 4:e982391; PMID:25949880; https://doi.org/10.4161/2162402X.2014.982391
30. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352:997-1003; PMID:15758010; https://doi.org/10.1056/NEJMoa043331
31. Wick W, Wick A, Platten M. Good maths is needed to understand CMV data in glioblastoma. Int J Cancer 2014; 134:2991-2; PMID:24248554; https://doi.org/10.1002/ijc.28614
32. Lilley BN, Ploegh HL. Viral modulation of antigen presentation:Manipulation of cellular targets in the ER and beyond. Immunol Rev 2005; 207:126-44; PMID:16181332; https://doi.org/10.1111/j.0105-2896.2005.00318.x
33. Lodoen MB, Lanier LL. Viral modulation of NK cell immunity. Nat Rev Microbiol 2005; 3:59-69; PMID:15608700; https://doi.org/10.1038/nrmicro1066
34. Slavuljica I, Krmpotic A, Jonjic S. Manipulation of NKG2D ligands by cytomegaloviruses:Impact on innate and adaptive immune response. Front Immunol 2011; 2:85; PMID:22566874; https://doi.org/10.3389/fimmu.2011.00085
35. Lucas KG, Bao L, Bruggeman R, Dunham K, Specht C. The detection of CMV pp65 and IE1 in glioblastoma multiforme. J Neurooncol 2011; 103:231-8; PMID:20820869; https://doi.org/10.1007/s11060-010-0383-6
36. Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, Sampson JH. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol 2008; 10:10-8; PMID:17951512; https://doi.org/10.1215/15228517-2007-035
37. Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol 2008; 116:79-86; PMID:18351367; https://doi.org/10.1007/s00401-008-0359-1
38. Ghazi A, Ashoori A, Hanley PJ, Brawley VS, Shaffer DR, Kew Y, Powell SZ, Grossman R, Grada Z, Scheurer ME, et al. Generation of polyclonal CMV-specific T cells for the adoptive immunotherapy of glioblastoma. J Immunother 2012; 35:159-68; PMID:22306904; https://doi.org/10.1097/CJI.0b013e318247642f
39. Morantz RA, Wood GW, Foster M, Clark M, Gollahon K. Macrophages in experimental and human brain tumors. Part 2:Studies of the macrophage content of human brain tumors. J Neurosurg 1979; 50:305-11; PMID:422981; https://doi.org/10.3171/jns.1979.50.3.0305
40. Siemens DR, Hu N, Sheikhi AK, Chung E, Frederiksen LJ, Pross H, Graham CH. Hypoxia increases tumor cell shedding of MHC class I chain-related molecule:Role of nitric oxide. Cancer Res 2008; 68:4746-53; PMID:18559521; https://doi.org/10.1158/0008-5472.CAN-08-0054
41. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392:245-52; PMID:9521319; https://doi.org/10.1038/32588
42. Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science 1996; 272:60-6; PMID:8600538; https://doi.org/10.1126/science.272.5258.60
43. Champagne P, Ogg GS, King AS, Knabenhans C, Ellefsen K, Nobile M, Appay V, Rizzardi GP, Fleury S, Lipp M, et al. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 2001; 410:106-11; PMID:11242051; https://doi.org/10.1038/35065118
44. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401:708-12; PMID:10537110; https://doi.org/10.1038/44385
45. Weninger W, Manjunath N, von Andrian UH. Migration and differentiation of CD8+ T cells. Immunol Rev 2002; 186:221-33; PMID:12234374; https://doi.org/10.1034/j.1600-065X.2002.18618.x
46. Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old:The Swedish longitudinal OCTO immune study. Mech Ageing Dev 2000; 121:187-201; PMID:11164473
47. Pedicord VA, Montalvo W, Leiner IM, Allison JP. Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance. Proc Natl Acad Sci U S A 2011; 108:266-71; PMID:21173239; https://doi.org/10.1073/pnas.1016791108
48. Almehmadi M, Hammad A, Heyworth S, Moberly J, Middleton D, Hopkins MJ, Hart IJ, Christmas SE. CD56+ T cells are increased in kidney transplant patients following cytomegalovirus infection. Transpl Infect Dis 2015; 17:518-26; PMID:26039898; https://doi.org/10.1111/tid.12405
49. Davis ZB, Cooley SA, Cichocki F, Felices M, Wangen R, Luo X, DeFor TE, Bryceson YT, Diamond DJ, Brunstein C, et al. Adaptive natural killer cell and killer cell immunoglobulin-like receptor-expressing T cell responses are induced by cytomegalovirus and are associated with protection against cytomegalovirus reactivation after allogeneic donor hematopoietic cell transplantation. Biol Blood Marrow Transplant 2015; 21:1653-62; PMID:26055301; https://doi.org/10.1016/j.bbmt.2015.05.025
50. Almehmadi M, Flanagan BF, Khan N, Alomar S, Christmas SE. Increased numbers and functional activity of CD56(+) T cells in healthy cytomegalovirus positive subjects. Immunology 2014; 142:258-68; PMID:24433347; https://doi.org/10.1111/imm.12250
51. Chan WK, Rujkijyanont P, Neale G, Yang J, Bari R, Das Gupta N, Holladay M, Rooney B, Leung W. Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and CD56+ T cells in human blood. J Immunol 2013; 191:1625-36; PMID:23858032; https://doi.org/10.4049/jimmunol.1300111
52. Chan DV, Gibson HM, Aufiero BM, Wilson AJ, Hafner MS, Mi QS, Wong HK. Differential CTLA-4 expression in human CD4+ versus CD8+ T cells is associated with increased NFAT1 and inhibition of CD4+ proliferation. Genes Immun 2014; 15:25-32; PMID:24173147; https://doi.org/10.1038/gene.2013.57
53. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways:Similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016; 39:98-106; PMID:26558876; https://doi.org/10.1097/COC.0000000000000239
54. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26:677-704; PMID:18173375; https://doi.org/10.1146/annurev.immunol.26.021607.090331
55. Wherry EJ. T cell exhaustion. Nat Immunol 2011; 12:492-9; PMID:21739672; https://doi.org/10.1038/ni.2035
56. Gras Navarro A, Bjorklund AT, Chekenya M. Therapeutic potential and challenges of natural killer cells in treatment of solid tumors. Front Immunol 2015; 6:202; PMID:25972872; https://doi.org/10.3389/fimmu.2015.00202
57. Kmiecik J, Poli A, Brons NH, Waha A, Eide GE, Enger, PØ, Zimmer J, Chekenya M. Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol 2013; 264:71-83; PMID:24045166; https://doi.org/10.1016/j.jneuroim.2013.08.013
58. Crough T, Beagley L, Smith C, Jones L, Walker DG, Khanna R. Ex vivo functional analysis, expansion and adoptive transfer of cytomegalovirus-specific T-cells in patients with glioblastoma multiforme. Immunol Cell Biol 2012; 90:872-80; PMID:22508289; https://doi.org/10.1038/icb.2012.19
59. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363:711-23; PMID:20525992; https://doi.org/10.1056/NEJMoa1003466
60. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364:2517-26; PMID:21639810; https://doi.org/10.1056/NEJMoa1104621
61. Robert L, Tsoi J, Wang X, Emerson R, Homet B, Chodon T, Mok S, Huang RR, Cochran AJ, Comin-Anduix B, et al. CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Clin Cancer Res 2014; 20:2424-32; PMID:24583799; https://doi.org/10.1158/1078-0432.CCR-13-2648
62. Yuan J, Ginsberg B, Page D, Li Y, Rasalan T, Gallardo HF, Xu Y, Adams S, Bhardwaj N, Busam K, et al. CTLA-4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma:Three cases. Cancer Immunol Immunother 2011; 60:1137-46; PMID:21465316; https://doi.org/10.1007/s00262-011-1011-9
63. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372:320-30; PMID:25399552; https://doi.org/10.1056/NEJMoa1412082
64. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372:2521-32; PMID:25891173; https://doi.org/10.1056/NEJMoa1503093
65. Muntasell A, Vilches C, Angulo A, Lopez-Botet M. Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus:A different perspective of the host-pathogen interaction. Eur J Immunol 2013; 43:1133-41; PMID:23552990; https://doi.org/10.1002/eji.201243117
66. Dominguez-Valentin M, Gras Navarro A, Rahman AM, Kumar S, Retière C, Ulvestad E, Kristensen V, Lund-Johansen M, Lie BA, Enger PØ, et al. Identification of a natural killer cell receptor allele that prolongs survival of cytomegalovirus-positive glioblastoma patients. Cancer Res 2016; 76(18):5326-36; PMID:27406829; https://doi.org/10.1158/0008-5472.CAN-16-1162
67. Lopez-Verges S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, Norris PJ, Nixon DF, Lanier LL. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 2010; 116:3865-74; PMID:20733159; https://doi.org/10.1182/blood-2010-04-282301
68. Rahbar A, Orrego A, Peredo I, Dzabic M, Wolmer-Solberg N, Strååt K, Stragliotto G, Söderberg-Nauclér C. Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival. J Clin Virol 2013; 57:36-42; PMID:23391370; https://doi.org/10.1016/j.jcv.2012.12.018
69. Griscelli F, Barrois M, Chauvin S, Lastere S, Bellet D, Bourhis JH. Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR. J Clin Microbiol 2001; 39:4362-9; PMID:11724846; https://doi.org/10.1128/JCM.39.12.4362-4369.2001
70. Habbal W, Monem F, Gartner BC. Comparative evaluation of published cytomegalovirus primers for rapid real-time PCR:Which are the most sensitive? J Med Microbiol 2009; 58:878-83; PMID:19502375; https://doi.org/10.1099/jmm.0.010587-0
71. Wada K, Kubota N, Ito Y, Yagasaki H, Kato K, Yoshikawa T, Ono Y, Ando H, Fujimoto Y, Kiuchi T, et al. Simultaneous quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 DNA in samples from transplant recipients by multiplex real-time PCR assay. J Clin Microbiol 2007; 45:1426-32; PMID:17376882; https://doi.org/10.1128/JCM.01515-06
72. Edvardsen K, Hellesen A, Husebye ES, Bratland E. Analysis of cellular and humoral immune responses against cytomegalovirus in patients with autoimmune Addison's disease. J Transl Med 2016; 14:68; PMID:26956521; https://doi.org/10.1186/s12967-016-0822-z