CD56bright NK cells exhibit potent antitumor responses following IL-15 priming

Journal of Clinical Investigation

Volumn 127, Issue 11, 2017, Pages 4042-4058

  Wagner, Julia A ^a   Rosario, Maximillian ^a   Romee, Rizwan ^a   Berrien Elliott, Melissa M ^a   Schneider, Stephanie E ^a   Leong, Jeffrey W ^a   Sullivan, Ryan P ^a,f   Jewell, Brea A ^a   Becker Hapak, Michelle ^a   Schappe, Timothy ^a   Abdel Latif, Sara ^a   Ireland, Aaron R ^a   Jaishankar, Devika ^a   King, Justin A ^a   Vij, Ravi ^a   Clement, Dennis ^b,c   Goodridge, Jodie ^b   Malmberg, Karl Johan ^b,c,d   Wong, Hing C ^e   Fehniger, Todd A ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c UNIVERSITY OF OSLO   (Norway)

^d KAROLINSKA INSTITUTE   (Sweden)

^e Altor BioScience   (United States)

^f NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD2 ANTIGEN; CD56 ANTIGEN; CELL ADHESION MOLECULE; CYTOTOXIC FACTOR; GAMMA INTERFERON; INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR; JANUS KINASE; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 2; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 3; NATURAL KILLER CELL RECEPTOR NKG2D; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAF PROTEIN; RAS PROTEIN; STAT PROTEIN; STAT5 PROTEIN; TUMOR NECROSIS FACTOR; ALT-803; IMMUNOLOGIC FACTOR; INTEGRIN; NCAM1 PROTEIN, HUMAN; PROTEIN;

ACUTE MYELOID LEUKEMIA; AKT/MTOR SIGNALING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER PATIENT; CELL FUNCTION; CONJUGATION; CONTROLLED STUDY; CROSS PRESENTATION; CYTOKINE PRODUCTION; CYTOKINE RESPONSE; CYTOTOXICITY; DEGRANULATION; EX VIVO STUDY; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; JAK-STAT SIGNALING; LEUKEMIA CELL; LYMPHOCYTE ACTIVATION; MALE; MAPK SIGNALING; MOUSE; MULTIPLE MYELOMA; NATURAL KILLER CELL; NONHUMAN; PI3K/AKT SIGNALING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; TUMOR IMMUNITY; ANIMAL; CANCER TRANSPLANTATION; COCULTURE; IMMUNOTHERAPY; INNATE IMMUNITY; K-562 CELL LINE; METABOLISM; NONOBESE DIABETIC MOUSE; PHYSIOLOGY; SCID MOUSE; SIGNAL TRANSDUCTION;

ANIMALS; CD56 ANTIGEN; CELL DEGRANULATION; COCULTURE TECHNIQUES; CYTOTOXICITY, IMMUNOLOGIC; HUMANS; IMMUNITY, INNATE; IMMUNOLOGIC FACTORS; IMMUNOTHERAPY; INTEGRINS; INTERLEUKIN-15; K562 CELLS; KILLER CELLS, NATURAL; LEUKEMIA, MYELOID, ACUTE; MICE, INBRED NOD; MICE, SCID; MULTIPLE MYELOMA; NEOPLASM TRANSPLANTATION; PROTEINS; SIGNAL TRANSDUCTION;

EID: 85032967284     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI90387     Document Type: Article

References (84)

1. Caligiuri MA. Human natural killer cells. Blood. 2008;112(3):461-469.
2. Lanier LL. NK cell recognition. Annu Rev Immunol. 2005;23:225-274.
3. Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol. 2013;31:227-258.
4. Min-Oo G, Kamimura Y, Hendricks DW, Nabekura T, Lanier LL. Natural killer cells: walking three paths down memory lane. Trends Immunol. 2013;34(6):251-258.
5. Vidal SM, Khakoo SI, Biron CA. Natural killer cell responses during viral infections: flexibility and conditioning of innate immunity by experience. Curr Opin Virol. 2011;1(6):497-512.
6. Jonsson AH, Yokoyama WM. Natural killer cell tolerance licensing and other mechanisms. Adv Immunol. 2009;101:27-79.
7. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633-640.
8. Freud AG, Caligiuri MA. Human natural killer cell development. Immunol Rev. 2006;214:56-72.
9. Fehniger TA, et al. CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood. 2003;101(8):3052-3057.
10. Ferlazzo G, et al. The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. J Immunol. 2004;172(3):1455-1462.
11. Ferlazzo G, 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):16606-16611.
12. Fehniger TA, et al. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J Immunol. 1999;162(8):4511-4520.
13. Cooper MA, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood. 2001;97(10):3146-3151.
14. Ruggeri L, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097-2100.
15. Miller JS, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051-3057.
16. Rubnitz JE, et al. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol. 2010;28(6):955-959.
17. Ljunggren HG, Malmberg KJ. Prospects for the use of NK cells in immunotherapy of human cancer. Nat Rev Immunol. 2007;7(5):329-339.
18. Berrien-Elliott MM, Romee R, Fehniger TA. Improving natural killer cell cancer immunotherapy. Curr Opin Organ Transplant. 2015;20(6):671-680.
19. Cooley S, et al. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood. 2009;113(3):726-732.
20. Venstrom JM, et al. HLA-C-dependent prevention of leukemia relapse by donor activating KIR2DS1. N Engl J Med. 2012;367(9):805-816.
21. Cooley S, et al. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood. 2010;116(14):2411-2419.
22. Fehniger TA, Caligiuri MA. Interleukin 15: biology and relevance to human disease. Blood. 2001;97(1):14-32.
23. Budagian V, Bulanova E, Paus R, Bulfone-Paus S. IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev. 2006;17(4):259-280.
24. Mishra A, Sullivan L, Caligiuri MA. Molecular pathways: interleukin-15 signaling in health and in cancer. Clin Cancer Res. 2014;20(8):2044-2050.
25. Fehniger TA, Cooper MA, Caligiuri MA. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 2002;13(2):169-183.
26. Koreth J, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365(22):2055-2066.
27. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12(3):180-190.
28. Fehniger TA, et al. Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs. Immunity. 2007;26(6):798-811.
29. Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity. 2007;26(4):503-517.
30. Nielsen CM, White MJ, Goodier MR, Riley EM. Functional significance of CD57 expression on human NK cells and relevance to disease. Front Immunol. 2013;4:422.
31. Huntington ND, Vosshenrich CA, Di Santo JP. Developmental pathways that generate naturalkiller-cell diversity in mice and humans. Nat Rev Immunol. 2007;7(9):703-714.
32. Amir el-AD, et al. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat Biotechnol. 2013;31(6):545-552.
33. Orange JS. Formation and function of the lytic NK-cell immunological synapse. Nat Rev Immunol. 2008;8(9):713-725.
34. Jacobs R, et al. CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells. Eur J Immunol. 2001;31(10):3121-3127.
35. Lincz LF, Yeh TX, Spencer A. TRAIL-induced eradication of primary tumour cells from MM patient bone marrows is not related to TRAIL receptor expression or prior chemotherapy. Leukemia. 2001;15(10):1650-1657.
36. Plasilova M, et al. TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors. Leukemia. 2002;16(1):67-73.
37. Anguille S, et al. Interleukin-15 dendritic cells harness NK cell cytotoxic effector function in a contact-and IL-15-dependent manner. PLoS One. 2015;10(5):e0123340.
38. Keating SE, et al. Metabolic reprogramming supports IFN-? production by CD56bright NK cells. J Immunol. 2016;196(6):2552-2560.
39. Mace EM, et al. Cell biological steps and checkpoints in accessing NK cell cytotoxicity. Immunol Cell Biol. 2014;92(3):245-255.
40. Barber DF, Faure M, Long EO. LFA-1 contributes an early signal for NK cell cytotoxicity. J Immunol. 2004;173(6):3653-3659.
41. Abram CL, Lowell CA. The ins and outs of leukocyte integrin signaling. Annu Rev Immunol. 2009;27:339-362.
42. Urlaub D, Hofer K, Muller ML, Watzl C. LFA-1 activation in NK cells and their subsets: influence of receptors, maturation, and cytokine stimulation. J Immunol. 2017;198(5):1944-1951.
43. Perez OD, Mitchell D, Jager GC, Nolan GP. LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells. Blood. 2004;104(4):1083-1093.
44. Waldmann TA. Interleukin-15 in the treatment of cancer. Expert Rev Clin Immunol. 2014;10(12):1689-1701.
45. Conlon KC, et al. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-inhuman clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015;33(1):74-82.
46. Rhode PR, et al. Comparison of the superagonist complex, ALT-803, to IL15 as cancer immunotherapeutics in animal models. Cancer Immunol Res. 2016;4(1):49-60.
47. Rosario M, et al. The IL-15-based ALT-803 complex enhances Fc?RIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas. Clin Cancer Res. 2016;22(3):596-608.
48. Zhu X, et al. Novel human interleukin-15 agonists. J Immunol. 2009;183(6):3598-3607.
49. Nandagopal N, Ali AK, Komal AK, Lee SH. The critical role of IL-15-PI3K-mTOR pathway in natural killer cell effector functions. Front Immunol. 2014;5:187.
50. Marcais A, et al. The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells. Nat Immunol. 2014;15(8):749-757.
51. Reynolds AM. The Cahn-Hilliard phase separation principle maybe the tip of an iceberg: comment on "Phase separation driven by densitydependent movement: a novel mechanism for ecological patterns" by
52. Q.-X. Liu et al. Phys Life Rev. 2016;19:135-136.
53. Romee R, Leong JW, Fehniger TA. Utilizing cytokines to function-enable human NK cells for the immunotherapy of cancer. Scientifica (Cairo). 2014;2014:205796.
54. Romee R, et al. Cytokine activation induces human memory-like NK cells. Blood. 2012;120(24):4751-4760.
55. Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM. Cytokine-induced memorylike natural killer cells. Proc Natl Acad Sci U S A. 2009;106(6):1915-1919.
56. Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med. 2012;209(13):2351-2365.
57. Romee R, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016;8(357):357ra123.
58. Benjamin JE, Gill S, Negrin RS. Biology and clinical effects of natural killer cells in allogeneic transplantation. Curr Opin Oncol. 2010;22(2):130-137.
59. Messaoudene M, 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.
60. Strowig T, et al. Tonsilar NK cells restrict B cell transformation by the Epstein-Barr virus via IFN-?. PLoS Pathog. 2008;4(2):e27.
61. Briard D, Brouty-Boye D, Azzarone B, Jasmin C. Fibroblasts from human spleen regulate NK cell differentiation from blood CD34(+) progenitors via cell surface IL-15. J Immunol. 2002;168(9):4326-4332.
62. Soderquest K, et al. Monocytes control natural killer cell differentiation to effector phenotypes. Blood. 2011;117(17):4511-4518.
63. Robertson MJ, et al. Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF. J Exp Med. 1992;175(3):779-788.
64. Takahashi E, et al. Induction of CD16+ CD56bright NK cells with antitumour cytotoxicity not only from CD16-CD56bright NK cells but also from CD16-CD56dim NK cells. Scand J Immunol. 2007;65(2):126-138.
65. Nielsen N, Odum N, Urso B, Lanier LL, Spee P. Cytotoxicity of CD56(bright) NK cells towards autologous activated CD4+ T cells is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A. PLoS One. 2012;7(2):e31959.
66. Mao Y, et al. IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells. Blood. 2016;128(11):1475-1489.
67. Trotta R, et al. Differential expression of SHIP1 in CD56bright and CD56dim NK cells provides a molecular basis for distinct functional responses to monokine costimulation. Blood. 2005;105(8):3011-3018.
68. Briercheck EL, et al. PTEN is a negative regulator of NK cell cytolytic function. J Immunol. 2015;194(4):1832-1840.
69. Grzywacz B, Miller JS, Verneris MR. Use of natural killer cells as immunotherapy for leukaemia. Best Pract Res Clin Haematol. 2008;21(3):467-483.
70. Zhang H, et al. Activating signals dominate inhibitory signals in CD137L/IL-15 activated natural killer cells. J Immunother. 2011;34(2):187-195.
71. Cooley S, et al. Recombinant human IL-15 promotes in vivo expansion of adoptively transferred NK cells in a first-in-human phase I dose escalation study in patients with AML. Blood. 2012;120(21):A894.
72. Rosario M, et al. The IL-15-based ALT-803 complex enhances Fc?RIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas. Clin Cancer Res. 2016;22(3):596-608.
73. Rhode PR, et al. Comparison of the superagonist complex, ALT-803, to IL15 as cancer immunotherapeutics in animal models. Cancer Immunol Res. 2016;4(1):49-60.
74. Nguyen S, et al. NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibmitory effect of NKG2A override GvL effect. Blood. 2005;105(10):4135-4142.
75. Yu J, et al. Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation. Blood. 2009;113(16):3875-3884.
76. Bjorklund AT, et al. NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLAmatched sibling stem cell transplantation. Blood. 2010;115(13):2686-2694.
77. Vukicevic M, et al. CD56bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells. Eur J Immunol. 2010;40(11):3246-3254.
78. Foley B, et al. Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function. Blood. 2012;119(11):2665-2674.
79. Dulphy N, et al. An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation. J Immunol. 2008;181(3):2227-2237.
80. Sarhan D, et al. Activated monocytes augment TRAIL-mediated cytotoxicity by human NK cells through release of IFN-?. Eur J Immunol. 2013;43(1):249-257.
81. Wennerberg E, et al. Doxorubicin sensitizes human tumor cells to NK cell-and T-cell-mediated killing by augmented TRAIL receptor signaling. Int J Cancer. 2013;133(7):1643-1652.
82. Zheng X, Wang Y, Wei H, Sun R, Tian Z. LFA-1 and CD2 synergize for the Erk1/2 activation in the natural killer (NK) cell immunological synapse. J Biol Chem. 2009;284(32):21280-21287.
83. Dransfield I, Hogg N. Regulated expression of Mg2+ binding epitope on leukocyte integrin ? subunits. EMBO J. 1989;8(12):3759-3765.
84. Dubois S, et al. IL15 infusion of cancer patients expands the subpopulation of cytotoxic CD56bright NK cells and increases NK cell cytokine release capabilities [published online ahead of print August 25, 2017]. Cancer Immunol Res. https:// doi. org/10. 1158/2326-6066. CIR-17-0279.