JAK inhibition impairs NK cell function in myeloproliferative neoplasms

Cancer Research

Volumn 75, Issue 11, 2015, Pages 2187-2199

  Schönberg, Kathrin ^a   Rudolph, Janna ^a   Vonnahme, Maria ^a   Yajnanarayana, Sowmya Parampalli ^a   Cornez, Isabelle ^a   Hejazi, Maryam ^b   Manser, Angela R ^b   Uhrberg, Markus ^b   Verbeek, Walter ^c   Koschmieder, Steffen ^d   Brümmendorf, Tim H ^d   Brossart, Peter ^a   Heine, Annkristin ^a   Wolf, Dominik ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^c ZAHO   (Germany)

^d RWTH AACHEN UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE; RUXOLITINIB; STAT PROTEIN; JAK3 PROTEIN, HUMAN; JANUS KINASE 3; PYRAZOLE DERIVATIVE;

ADULT; ARTICLE; BACTERIAL INFECTION; CELL COUNT; CELL MATURATION; CELL PROLIFERATION; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG RESPONSE; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; IMMUNOLOGICAL SYNAPSE; IN VITRO STUDY; IN VIVO STUDY; INFECTION RATE; MALE; MYCOSIS; MYELOPROLIFERATIVE NEOPLASM; NATURAL KILLER CELL; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; VIRUS INFECTION; AGED; ANTAGONISTS AND INHIBITORS; BONE MARROW NEOPLASMS; DRUG EFFECTS; GENETICS; MIDDLE AGED; NEOPLASMS; PATHOLOGY; PRIMARY MYELOFIBROSIS; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; BONE MARROW NEOPLASMS; CELL PROLIFERATION; FEMALE; HUMANS; JANUS KINASE 3; KILLER CELLS, NATURAL; MALE; MIDDLE AGED; NEOPLASMS; PRIMARY MYELOFIBROSIS; PYRAZOLES; SIGNAL TRANSDUCTION;

EID: 84939429649     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-14-3198     Document Type: Article

References (50)

1. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med 2000; 342:1255-65.
2. Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem 2007; 282:20059-63.
3. Percy MJ, McMullin MF The V617F JAK2 mutation and the myeloprolif-erative disorders. Hematol Oncol 2005; 23:91-3.
4. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H., Waltzman R, Stalbovskaya V, et al JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012; 366:787-98.
5. Verstovsek S, Mesa RA, Gotlib J, Levy R.S., Gupta V., DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366:799-807.
6. Santos FP, Verstovsek S. JAK2 inhibitors for myelofibrosis: why are they effective in patients with and without JAK2V617F mutation? Anti-cancer Agents Med Chem 2012; 12:1098-109.
7. Colomba C, Rubino R, Siracusa L., Lalicata F, Trizzino M, Titone L., et al. Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report. BMC Res Notes 2012; 5:552.
8. Hopman RK, Lawrence SJ, Oh ST Disseminated tuberculosis associated with ruxolitinib. Leukemia 2014; 28:1750-1.
9. Caocci G, Murgia F, Podda L., Solinas A, Atzeni S, La Nasa G. Reactivation of hepatitis B virus infection following ruxolitinib treatment in a patient with myelofibrosis. Leukemia 2014; 28:225-7.
10. Wathes R, Moule S, Milojkovic D. Progressive multifocal leukoencephalo-pathy associated with ruxolitinib. N Engl J Med 2013; 369:197-8.
11. Goldberg RA, Reichel E, Oshry LJ Bilateral toxoplasmosis retinitis associated with ruxolitinib. N Engl J Med 2013; 369:681-3.
12. Hurwitz H, Uppal N, Wagner S.A., Bendell JC, Beck JT, Wade S, et al A randomized double-blind phase 2 study of ruxolitinib (RUX) or placebo (PBO) with capecitabine (CAPE) as second-line therapy in patients (pts) with metastatic pancreatic cancer (mPC). J Clin Oncol 2014; 32:5s, 2014 (suppl; abstr 4000).
13. Heine A, Held SA, Daecke S.N., Wallner S., Yajnanarayana SP, Kurts C, et al. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood 2013; 122:1192-202.
14. Vivier E, Tomasello E, Baratin M., Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol 2008; 9:503-10.
15. Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 2008; 9:495-502.
16. Ortmann RA, Cheng T, Visconti R., Frucht DM, O'Shea JJ. Janus kinases and signal transducers and activators of transcription: their roles in cytokine signaling, development and immunoregulation. Arthritis Res 2000; 2:16-32.
17. Schonberg K, Hejazi M, Uhrberg M. Protocol for the clonal analysis of NK cell effector functions by multi-parameter flow cytometry. Methods Mol Biol 2012; 903:381-92.
18. Schonberg K, Sribar M, Enczmann J., Fischer JC, Uhrberg M. Analyses of HLA-C-specific KIR repertoires in donors with group A and B haplotypes suggest a ligand-instructed model of NK cell receptor acquisition. Blood 2011; 117:98-107.
19. Cornez I, Joel M, Tasken K, Langmoen IA, Glover JC, Berge T. EGFsignalling and rapamycin-mediated mTOR inhibition in glioblastoma multiforme evaluated by phospho-specific flow cytometry. J Neurooncol 2013; 112: 49-57.
20. Hazeldine J, Lord JM The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev 2013; 12:1069-78.
21. Fu B, Wang F, Sun R, Ling B, Tian Z, Wei H. CD11b and CD27 reflectdistinct population and functional specialization in human natural killer cells. Immunology 2011; 133:350-9.
22. Chiossone L, Chaix J, Fuseri N., Roth C, Vivier E, Walzer T. Maturation of mouse NK cells is a 4-stage developmental program. Blood 2009; 113: 5488-96.
23. Juelke K, Killig M, Thiel A., Dong J, Romagnani C. Education of hyporesponsive NK cells by cytokines. Eur J Immunol 2009; 39: 2548-55.
24. Anfossi N, Andre P, Guia S., Falk CS, Roetynck S, Stewart CA, et al Human NK cell education by inhibitory receptors for MHC class I. Immunity 2006; 25:331-42.
25. Shilling AD, Nedza FM, Emm T, Diamond S., McKeever E, Punwani N, et al Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus tyrosine kinase 1/2 inhibitor, in humans. Drug Metab Dispos 2010; 38:2023-31.
26. Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc 2011; 86:1188-91.
27. Colucci F, Caligiuri MA, Di Santo JP. What does it take to make a natural killer? Nat Rev Immunol 2003; 3:413-25.
28. Miller JS, McCullar V. Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2. Blood 2001; 98:705-13.
29. Gilmour KC, Fujii H, Cranston T., Davies EG, Kinnon C, Gaspar HB. Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency. Blood 2001; 98:877-9.
30. Cooper MA, Bush JE, Fehniger T.A., VanDeusen JB, Waite RE, Liu Y, et al In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 2002; 100:3633-8.
31. Vosshenrich CA, Ranson T, Samson S.I., Corcuff E., Colucci F, Rosmaraki EE, et al Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J Immunol 2005; 174: 1213-21.
32. Ranson T, Vosshenrich CA, Corcuff E, Richard O., Muller W, Di Santo JP. IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood 2003; 101:4887-93.
33. Roberts JL, Lengi A, Brown S.M., Chen M., Zhou YJ, O'Shea JJ, et al. Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Blood 2004; 103:2009-18.
34. Bernasconi A, Marino R, Ribas A., Rossi J, Ciaccio M, Oleastro M., et al. Characterization of immunodeficiency in a patient with growth hormone insensitivity secondary to a novel STAT5b gene mutation. Pediatrics 2006; 118:e1584-92.
35. Lin JX, Leonard WJ The role of Stat5a and Stat5b in signaling by IL-2 family cytokines. Oncogene 2000; 19:2566-76.
36. Quintas-Cardama A., Vaddi K, Liu P., Manshouri T, Li J, Scherle P.A., et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010; 115:3109-17.
37. Zhou T, Georgeon S, Moser R., Moore DJ, Caflisch A, Hantschel O. Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348). Leukemia 2014; 28:471-2.
38. Gorantla SP B.K., Illert AL, von Bubnoff N, Peschel C, Duyster J. Ruxolitinib mediated paradox JAK2 hyperphosphorylation is due to the protection of activation loop phosphotyrosines from phosphatases. ASH 2013 2013; abstr 2847.
39. Bogani C, Guglielmelli P, Antonioli E., Pancrazzi A, Bosi A, Vannucchi AM B-, T-, and NK-cell lineage involvement in JAK2V617F-positive patients with idiopathic myelofibrosis. Haematologica 2007; 92:258-9.
40. Froom P, Aghai E, Kinarty A., Lahat N. Decreased natural killer (NK) activity in patients with myeloproliferative disorders. Cancer 1989; 64:1038-40.
41. Gersuk GM, Carmel R, Pattamakom S., Challita PM, Rabinowitz AP, Pattengale PK. Quantitative and functional studies of impaired natural killer (NK) cells in patients with myelofibrosis, essential thrombo-cythemia, and polycythemia vera. I. A potential role for platelet-derived growth factor in defective NK cytotoxicity. Nat Immun 1993; 12:136-51.
42. Almeida-Oliveira A., Smith-Carvalho M, Porto L.C., Cardoso-Oliveira J, Ribeiro Ados S, Falcao RR, et al Age-related changes in natural killer cell receptors from childhood through old age. Hum Immunol 2011; 72: 319-29.
43. Orange JS. Formation and function of the lytic NK-cell immunological synapse. Nat Rev Immunol 2008; 8:713-25.
44. Bellucci R, Nguyen HN, Martin A, Heinrichs S., Schinzel AC, Hahn WC, et al. Tyrosine kinase pathways modulate tumor susceptibility to natural killer cells. J Clin Invest 2012; 122:2369-83.
45. Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S., Mueller T, et al. Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood 2014; 123:3832-42.
46. Ruggeri L, Capanni M, Urbani E., Perruccio K, Shlomchik WD, Tosti A, et al Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097-100.
47. Jost S, Altfeld M. Control of human viral infections by natural killer cells. Annu Rev Immunol 2013; 31:163-94.
48. Orange JS. Natural killer cell deficiency. J Allergy Clin Immunol 2013; 132:515-25; quiz 26.
49. Tong LX, Jackson J, Kerstetter J., Worswick SD. Reactivation of herpes simplex virus infection in a patient undergoing ruxolitinib treatment. J Am Acad Dermatol 2014; 70:e59-60.
50. Parampalli Yajnanarayana S., Stübig T, Cornez I., Alchalby H, Schönberg K, Rudolph J., et al. JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms. Br J Haematol 2015 Mar 30. doi:10.1111/bjh.13373. [Epub ahead of print].