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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 4/2016

01-04-2016 | Symposium-in-writing paper

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

Authors: Gabriella Pietra, Chiara Vitale, Daniela Pende, Alice Bertaina, Francesca Moretta, Michela Falco, Paola Vacca, Elisa Montaldo, Claudia Cantoni, Maria Cristina Mingari, Alessandro Moretta, Franco Locatelli, Lorenzo Moretta

Published in: Cancer Immunology, Immunotherapy | Issue 4/2016

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Abstract

It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host’s defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment.
Literature
1.
Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331(6013):44–49PubMedPubMedCentralCrossRef
2.
3.
Cerwenka A, Lanier LL (2001) Natural killer cells, viruses and cancer. Nat Rev Immunol 1(1):41–49PubMedCrossRef
4.
Fauriat C, Long EO, Ljunggren HG, Bryceson YT (2010) Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood 115(11):2167–2176PubMedPubMedCentralCrossRef
5.
Bryceson YT, March ME, Ljunggren HG, Long EO (2006) Activation, coactivation, and costimulation of resting human natural killer cells. Immunol Rev 214:73–91PubMedCrossRef
6.
Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC, Moretta L (1996) Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol 14:619–648PubMedCrossRef
7.
Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223PubMedCrossRef
8.
Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A (2002) Human natural killer cells: their origin, receptors and function. Eur J Immunol 32(5):1205–1211PubMedCrossRef
9.
Moretta L, Bottino C, Pende D, Vitale M, Mingari MC, Moretta A (2004) Different checkpoints in human NK-cell activation. Trends Immunol 25(12):670–676PubMedCrossRef
10.
Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22(11):633–640PubMedCrossRef
11.
12.
Montaldo E, Del Zotto G, Della Chiesa M, Mingari MC, Moretta A, De Maria A, Moretta L (2013) Human NK cell receptors/markers: a tool to analyze NK cell development, subsets and function. Cytometry A 83(8):702–713PubMedCrossRef
13.
Carrega P, Bonaccorsi I, Di Carlo E, Morandi B, Paul P, Rizzello V, Cipollone G, Navarra G, Mingari MC, Moretta L, Ferlazzo G (2014) 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 192(8):3805–3815PubMedCrossRef
14.
15.
Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, Powrie F, Vivier E (2013) Innate lymphoid cells—a proposal for uniform nomenclature. Nat Rev Immunol 13(2):145–149PubMedCrossRef
16.
Eberl G, Di Santo JP, Vivier E (2015) The brave new world of innate lymphoid cells. Nat Immunol 16(1):1–5PubMedCrossRef
17.
Bernink JH, Peters CP, Munneke M, te Velde AA, Meijer SL, Weijer K, Hreggvidsdottir HS, Heinsbroek SE, Legrand N, Buskens CJ, Bemelman WA, Mjosberg JM, Spits H (2013) Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol 14(3):221–229PubMedCrossRef
18.
Fuchs A, Vermi W, Lee JS, Lonardi S, Gilfillan S, Newberry RD, Cella M, Colonna M (2013) Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity 38(4):769–781PubMedPubMedCentralCrossRef
19.
20.
Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Setoyama H, Imaoka A, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H (2014) Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science 345(6202):1254009PubMedPubMedCentralCrossRef
21.
Vacca P, Montaldo E, Croxatto D, Loiacono F, Canegallo F, Venturini PL, Moretta L, Mingari MC (2015) Identification of diverse innate lymphoid cells in human decidua. Mucosal Immunol 8(2):254–264PubMedCrossRef
22.
Dyring-Andersen B, Geisler C, Agerbeck C, Lauritsen JP, Gudjonsdottir SD, Skov L, Bonefeld CM (2014) Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin. Br J Dermatol 170(3):609–616PubMedCrossRef
23.
Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F, Szabady RL, Harrison O, Powrie F (2013) Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med 210(5):917–931PubMedPubMedCentralCrossRef
24.
Dieu-Nosjean MC, Goc J, Giraldo NA, Sautes-Fridman C, Fridman WH (2014) Tertiary lymphoid structures in cancer and beyond. Trends Immunol 35(11):571–580PubMedCrossRef
25.
Pitzalis C, Jones GW, Bombardieri M, Jones SA (2014) Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat Rev Immunol 14(7):447–462PubMedCrossRef
26.
Burke S, Lakshmikanth T, Colucci F, Carbone E (2010) New views on natural killer cell-based immunotherapy for melanoma treatment. Trends Immunol 31(9):339–345PubMedCrossRef
27.
Carrega P, Morandi B, Costa R, Frumento G, Forte G, Altavilla G, Ratto GB, Mingari MC, Moretta L, Ferlazzo G (2008) Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(−) cells and display an impaired capability to kill tumor cells. Cancer 112(4):863–875PubMedCrossRef
28.
Mamessier E, Sylvain A, Thibult ML, Houvenaeghel G, Jacquemier J, Castellano R, Goncalves A, Andre P, Romagne F, Thibault G, Viens P, Birnbaum D, Bertucci F, Moretta A, Olive D (2011) Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest 121(9):3609–3622PubMedPubMedCentralCrossRef
29.
Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, Andre P, Dieu-Nosjean MC, Alifano M, Regnard JF, Fridman WH, Sautes-Fridman C, Cremer I (2011) Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res 71(16):5412–5422PubMedCrossRef
30.
Konjevic G, Mirjacic Martinovic K, Vuletic A, Jovic V, Jurisic V, Babovic N, Spuzic I (2007) Low expression of CD161 and NKG2D activating NK receptor is associated with impaired NK cell cytotoxicity in metastatic melanoma patients. Clin Exp Metastasis 24(1):1–11PubMedCrossRef
31.
Lee JC, Lee KM, Kim DW, Heo DS (2004) Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J Immunol 172(12):7335–7340PubMedCrossRef
32.
Costello RT, Sivori S, Marcenaro E, Lafage-Pochitaloff M, Mozziconacci MJ, Reviron D, Gastaut JA, Pende D, Olive D, Moretta A (2002) Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood 99(10):3661–3667PubMedCrossRef
33.
Halama N, Braun M, Kahlert C, Spille A, Quack C, Rahbari N, Koch M, Weitz J, Kloor M, Zoernig I, Schirmacher P, Brand K, Grabe N, Falk CS (2011) Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. Clin Cancer Res 17(4):678–689PubMedCrossRef
34.
Balsamo M, Scordamaglia F, Pietra G, Manzini C, Cantoni C, Boitano M, Queirolo P, Vermi W, Facchetti F, Moretta A, Moretta L, Mingari MC, Vitale M (2009) Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. Proc Natl Acad Sci USA 106(49):20847–20852PubMedPubMedCentralCrossRef
35.
Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L, Moretta A (2003) Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA 100(7):4120–4125PubMedPubMedCentralCrossRef
36.
Pietra G, Manzini C, Rivara S, Vitale M, Cantoni C, Petretto A, Balsamo M, Conte R, Benelli R, Minghelli S, Solari N, Gualco M, Queirolo P, Moretta L, Mingari MC (2012) Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res 72(6):1407–1415PubMedCrossRef
37.
Marcenaro E, Della Chiesa M, Bellora F, Parolini S, Millo R, Moretta L, Moretta A (2005) IL-12 or IL-4 prime human NK cells to mediate functionally divergent interactions with dendritic cells or tumors. J Immunol 174(7):3992–3998PubMedCrossRef
38.
Ghiringhelli F, Menard C, Martin F, Zitvogel L (2006) The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression. Immunol Rev 214:229–238PubMedCrossRef
39.
Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J, Chaput N, Puig PE, Novault S, Escudier B, Vivier E, Lecesne A, Robert C, Blay JY, Bernard J, Caillat-Zucman S, Freitas A, Tursz T, Wagner-Ballon O, Capron C, Vainchencker W, Martin F, Zitvogel L (2005) CD4+ CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med 202(8):1075–1085PubMedPubMedCentralCrossRef
40.
Sitrin J, Ring A, Garcia KC, Benoist C, Mathis D (2013) Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2. J Exp Med 210(6):1153–1165PubMedPubMedCentralCrossRef
41.
Hoechst B, Voigtlaender T, Ormandy L, Gamrekelashvili J, Zhao F, Wedemeyer H, Lehner F, Manns MP, Greten TF, Korangy F (2009) Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50(3):799–807PubMedCrossRef
42.
Sprinzl MF, Reisinger F, Puschnik A, Ringelhan M, Ackermann K, Hartmann D, Schiemann M, Weinmann A, Galle PR, Schuchmann M, Friess H, Otto G, Heikenwalder M, Protzer U (2013) Sorafenib perpetuates cellular anticancer effector functions by modulating the crosstalk between macrophages and natural killer cells. Hepatology 57(6):2358–2368PubMedCrossRef
43.
Li T, Yang Y, Hua X, Wang G, Liu W, Jia C, Tai Y, Zhang Q, Chen G (2012) Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. Cancer Lett 318(2):154–161PubMedCrossRef
44.
Li T, Yi S, Liu W, Jia C, Wang G, Hua X, Tai Y, Zhang Q, Chen G (2013) Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity. Med Oncol 30(3):663PubMedCrossRef
45.
El-Gazzar A, Groh V, Spies T (2013) Immunobiology and conflicting roles of the human NKG2D lymphocyte receptor and its ligands in cancer. J Immunol 191(4):1509–1515PubMedPubMedCentralCrossRef
46.
Krockenberger M, Dombrowski Y, Weidler C, Ossadnik M, Honig A, Hausler S, Voigt H, Becker JC, Leng L, Steinle A, Weller M, Bucala R, Dietl J, Wischhusen J (2008) Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. J Immunol 180(11):7338–7348PubMedPubMedCentralCrossRef
47.
Gubbels JA, Felder M, Horibata S, Belisle JA, Kapur A, Holden H, Petrie S, Migneault M, Rancourt C, Connor JP, Patankar MS (2010) MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells. Mol Cancer 9:11PubMedPubMedCentralCrossRef
48.
Castriconi R, Dondero A, Bellora F, Moretta L, Castellano A, Locatelli F, Corrias MV, Moretta A, Bottino C (2013) Neuroblastoma-derived TGF-beta1 modulates the chemokine receptor repertoire of human resting NK cells. J Immunol 190(10):5321–5328PubMedCrossRef
49.
Balsamo M, Manzini C, Pietra G, Raggi F, Blengio F, Mingari MC, Varesio L, Moretta L, Bosco MC, Vitale M (2013) Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC. Eur J Immunol 43(10):2756–2764PubMedCrossRef
50.
Balsamo M, Vermi W, Parodi M, Pietra G, Manzini C, Queirolo P, Lonardi S, Augugliaro R, Moretta A, Facchetti F, Moretta L, Mingari MC, Vitale M (2012) 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 42(7):1833–1842PubMedCrossRef
51.
Pogge von Strandmann E, Simhadri VR, von Tresckow B, Sasse S, Reiners KS, Hansen HP, Rothe A, Boll B, Simhadri VL, Borchmann P, McKinnon PJ, Hallek M, Engert A (2007) Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity 27(6):965–974PubMedCrossRef
52.
Reiners KS, Topolar D, Henke A, Simhadri VR, Kessler J, Sauer M, Bessler M, Hansen HP, Tawadros S, Herling M, Kronke M, Hallek M, Pogge von Strandmann E (2013) Soluble ligands for NK cell receptors promote evasion of chronic lymphocytic leukemia cells from NK cell anti-tumor activity. Blood 121(18):3658–3665PubMedPubMedCentralCrossRef
53.
Rosental B, Brusilovsky M, Hadad U, Oz D, Appel MY, Afergan F, Yossef R, Rosenberg LA, Aharoni A, Cerwenka A, Campbell KS, Braiman A, Porgador A (2011) Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44. J Immunol 187(11):5693–5702PubMedPubMedCentralCrossRef
54.
Horton NC, Mathew SO, Mathew PA (2013) Novel interaction between proliferating cell nuclear antigen and HLA I on the surface of tumor cells inhibits NK cell function through NKp44. PLoS ONE 8(3):e59552PubMedPubMedCentralCrossRef
55.
Cantoni C, Bottino C, Augugliaro R, Morelli L, Marcenaro E, Castriconi R, Vitale M, Pende D, Sivori S, Millo R, Biassoni R, Moretta L, Moretta A (1999) Molecular and functional characterization of IRp60, a member of the immunoglobulin superfamily that functions as an inhibitory receptor in human NK cells. Eur J Immunol 29(10):3148–3159PubMedCrossRef
56.
Lankry D, Rovis TL, Jonjic S, Mandelboim O (2013) The interaction between CD300a and phosphatidylserine inhibits tumor cell killing by NK cells. Eur J Immunol 43(8):2151–2161PubMedCrossRef
57.
Sloma I, Jiang X, Eaves AC, Eaves CJ (2010) Insights into the stem cells of chronic myeloid leukemia. Leukemia 24(11):1823–1833PubMedCrossRef
58.
59.
60.
Wiseman DH, Greystoke BF, Somervaille TC (2014) The variety of leukemic stem cells in myeloid malignancy. Oncogene 33(24):3091–3098PubMedCrossRef
61.
Costello RT, Fauriat C, Sivori S, Marcenaro E, Olive D (2004) NK cells: innate immunity against hematological malignancies? Trends Immunol 25(6):328–333PubMedCrossRef
62.
Carlsten M, Baumann BC, Simonsson M, Jadersten M, Forsblom AM, Hammarstedt C, Bryceson YT, Ljunggren HG, Hellstrom-Lindberg E, Malmberg KJ (2010) Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34 + blasts in myelodysplastic syndrome. Leukemia 24(9):1607–1616PubMedCrossRef
63.
Stringaris K, Sekine T, Khoder A, Alsuliman A, Razzaghi B, Sargeant R, Pavlu J, Brisley G, de Lavallade H, Sarvaria A, Marin D, Mielke S, Apperley JF, Shpall EJ, Barrett AJ, Rezvani K (2014) Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia. Haematologica 99(5):836–847PubMedPubMedCentralCrossRef
64.
Curti A, Trabanelli S, Salvestrini V, Baccarani M, Lemoli RM (2009) The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood 113(11):2394–2401PubMedCrossRef
65.
Szczepanski MJ, Szajnik M, Welsh A, Whiteside TL, Boyiadzis M (2011) Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica 96(9):1302–1309PubMedPubMedCentralCrossRef
66.
Ayala F, Dewar R, Kieran M, Kalluri R (2009) Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia 23(12):2233–2241PubMedPubMedCentralCrossRef
67.
Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith RM, Qureshi A, Dazzi F, Vyas P, Cerundolo V (2013) Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood 122(5):749–758PubMedPubMedCentralCrossRef
68.
Duan CW, Shi J, Chen J, Wang B, Yu YH, Qin X, Zhou XC, Cai YJ, Li ZQ, Zhang F, Yin MZ, Tao Y, Mi JQ, Li LH, Enver T, Chen GQ, Hong DL (2014) Leukemia propagating cells rebuild an evolving niche in response to therapy. Cancer Cell 25(6):778–793PubMedCrossRef
69.
Tsimberidou AM, Estey E, Wen S, Pierce S, Kantarjian H, Albitar M, Kurzrock R (2008) The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes. Cancer 113(7):1605–1613PubMedCrossRef
70.
Kornblau SM, McCue D, Singh N, Chen W, Estrov Z, Coombes KR (2010) Recurrent expression signatures of cytokines and chemokines are present and are independently prognostic in acute myelogenous leukemia and myelodysplasia. Blood 116(20):4251–4261PubMedPubMedCentralCrossRef
71.
Vitale C, Ambrosini P, Montaldo E, Ballerini F, Moretta L, Mingari MC (2015) IL-1beta-releasing human acute myeloid leukemia blasts modulate natural killer cell differentiation from CD34 + precursors. Haematologica 100(2):e42–e45PubMedPubMedCentralCrossRef
72.
Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT et al (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313(23):1485–1492PubMedCrossRef
73.
Law TM, Motzer RJ, Mazumdar M, Sell KW, Walther PJ, O’Connell M, Khan A, Vlamis V, Vogelzang NJ, Bajorin DF (1995) Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer 76(5):824–832PubMedCrossRef
74.
Bordignon C, Carlo-Stella C, Colombo MP, De Vincentiis A, Lanata L, Lemoli RM, Locatelli F, Olivieri A, Rondelli D, Zanon P, Tura S (1999) Cell therapy: achievements and perspectives. Haematologica 84(12):1110–1149PubMed
75.
76.
Parkhurst MR, Riley JP, Dudley ME, Rosenberg SA (2011) Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Clin Cancer Res 17(19):6287–6297PubMedPubMedCentralCrossRef
77.
Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB (2005) Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105(8):3051–3057PubMedCrossRef
78.
Geller MA, Cooley S, Judson PL, Ghebre R, Carson LF, Argenta PA, Jonson AL, Panoskaltsis-Mortari A, Curtsinger J, McKenna D, Dusenbery K, Bliss R, Downs LS, Miller JS (2011) A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 13(1):98–107PubMedPubMedCentralCrossRef
79.
Iliopoulou EG, Kountourakis P, Karamouzis MV, Doufexis D, Ardavanis A, Baxevanis CN, Rigatos G, Papamichail M, Perez SA (2010) A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother 59(12):1781–1789PubMedCrossRef
80.
Wennerberg E, Kremer V, Childs R, Lundqvist A (2015) CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo. Cancer Immunol Immunother 64(2):225–235PubMedCrossRef
81.
Moustaki A, Argyropoulos KV, Baxevanis CN, Papamichail M, Perez SA (2011) Effect of the simultaneous administration of glucocorticoids and IL-15 on human NK cell phenotype, proliferation and function. Cancer Immunol Immunother 60(12):1683–1695PubMedCrossRef
82.
Vacca P, Martini S, Garelli V, Passalacqua G, Moretta L, Mingari MC (2013) NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short-term IL-2 activation. Eur J Immunol 43(2):550–561PubMedCrossRef
83.
Vacca P, Martini S, Mingari MC, Moretta L (2013) NK cells from malignant pleural effusions are potent antitumor effectors: a clue for adoptive immunotherapy? Oncoimmunology 2(4):e23638PubMedPubMedCentralCrossRef
84.
Terme M, Fridman WH, Tartour E (2013) NK cells from pleural effusions are potent antitumor effector cells. Eur J Immunol 43(2):331–334PubMedCrossRef
85.
Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A (2012) Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med 209(13):2351–2365PubMedPubMedCentralCrossRef
86.
Ardolino M, Azimi CS, Iannello A, Trevino TN, Horan L, Zhang L, Deng W, Ring AM, Fischer S, Garcia KC, Raulet DH (2014) Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. J Clin Invest 124(11):4781–4794PubMedPubMedCentralCrossRef
87.
Vacchelli E, Galluzzi L, Eggermont A, Galon J, Tartour E, Zitvogel L, Kroemer G (2012) Trial watch: immunostimulatory cytokines. Oncoimmunology 1(4):493–506PubMedPubMedCentralCrossRef
88.
Tarhini AA, Millward M, Mainwaring P, Kefford R, Logan T, Pavlick A, Kathman SJ, Laubscher KH, Dar MM, Kirkwood JM (2009) A phase 2, randomized study of SB-485232, rhIL-18, in patients with previously untreated metastatic melanoma. Cancer 115(4):859–868PubMedCrossRef
89.
Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, Fleisher TA, Dubois SP, Perera LP, Stewart DM, Goldman CK, Bryant BR, Decker JM, Chen J, Worthy TA, Figg WD Sr, Peer CJ, Sneller MC, Lane HC, Yovandich JL, Creekmore SP, Roederer M, Waldmann TA (2015) Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol 33(1):74–82PubMedPubMedCentralCrossRef
90.
Terme M, Ullrich E, Delahaye NF, Chaput N, Zitvogel L (2008) Natural killer cell-directed therapies: moving from unexpected results to successful strategies. Nat Immunol 9(5):486–494PubMedCrossRef
91.
92.
Romagne F, Andre P, Spee P, Zahn S, Anfossi N, Gauthier L, Capanni M, Ruggeri L, Benson DM Jr, Blaser BW, Della Chiesa M, Moretta A, Vivier E, Caligiuri MA, Velardi A, Wagtmann N (2009) Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood 114(13):2667–2677PubMedPubMedCentralCrossRef
93.
Kohrt HE, Thielens A, Marabelle A, Sagiv-Barfi I, Sola C, Chanuc F, Fuseri N, Bonnafous C, Czerwinski D, Rajapaksa A, Waller E, Ugolini S, Vivier E, Romagne F, Levy R, Blery M, Andre P (2014) Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood 123(5):678–686PubMedPubMedCentralCrossRef
94.
95.
Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B, Hodes MZ, Good RA, O’Reilly RJ (1983) Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 61(2):341–348PubMed
96.
Locatelli F, Merli P, Rutella S (2013) At the bedside: innate immunity as an immunotherapy tool for hematological malignancies. J Leukoc Biol 94(6):1141–1157PubMedCrossRef
97.
Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C, Iacucci R, Zei T, Martelli MP, Gambelunghe C et al (1994) Successful engraftment of T-cell-depleted haploidentical “three-loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood 84(11):3948–3955PubMed
98.
Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF (1998) Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 339(17):1186–1193PubMedCrossRef
99.
Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295(5562):2097–2100PubMedCrossRef
100.
Moretta L, Locatelli F, Pende D, Marcenaro E, Mingari MC, Moretta A (2011) Killer Ig-like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation. Blood 117(3):764–771PubMedCrossRef
101.
Locatelli F, Pende D, Mingari MC, Bertaina A, Falco M, Moretta A, Moretta L (2013) Cellular and molecular basis of haploidentical hematopoietic stem cell transplantation in the successful treatment of high-risk leukemias: role of alloreactive NK cells. Front Immunol 4:15PubMedPubMedCentralCrossRef
102.
Pende D, Bottino C, Castriconi R, Cantoni C, Marcenaro S, Rivera P, Spaggiari GM, Dondero A, Carnemolla B, Reymond N, Mingari MC, Lopez M, Moretta L, Moretta A (2005) PVR (CD155) and nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol 42(4):463–469PubMedCrossRef
103.
Pende D, Marcenaro S, Falco M, Martini S, Bernardo ME, Montagna D, Romeo E, Cognet C, Martinetti M, Maccario R, Mingari MC, Vivier E, Moretta L, Locatelli F, Moretta A (2009) Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood 113(13):3119–3129PubMedCrossRef
104.
Pende D, Spaggiari GM, Marcenaro S, Martini S, Rivera P, Capobianco A, Falco M, Lanino E, Pierri I, Zambello R, Bacigalupo A, Mingari MC, Moretta A, Moretta L (2005) Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the poliovirus receptor (CD155) and nectin-2 (CD112). Blood 105(5):2066–2073PubMedCrossRef
105.
Chewning JH, Gudme CN, Hsu KC, Selvakumar A, Dupont B (2007) KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol 179(2):854–868PubMedCrossRef
106.
Venstrom JM, Pittari G, Gooley TA, Chewning JH, Spellman S, Haagenson M, Gallagher MM, Malkki M, Petersdorf E, Dupont B, Hsu KC (2012) HLA-C-dependent prevention of leukemia relapse by donor activating KIR2DS1. N Engl J Med 367(9):805–816PubMedPubMedCentralCrossRef
107.
Symons HJ, Leffell MS, Rossiter ND, Zahurak M, Jones RJ, Fuchs EJ (2010) Improved survival with inhibitory killer immunoglobulin receptor (KIR) gene mismatches and KIR haplotype B donors after nonmyeloablative, HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant 16(4):533–542PubMedPubMedCentralCrossRef
108.
Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SG, Geraghty D, Spellman S, Haagenson MD, Ladner M, Trachtenberg E, Parham P, Miller JS (2010) Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood 116(14):2411–2419PubMedPubMedCentralCrossRef
109.
Oevermann L, Michaelis SU, Mezger M, Lang P, Toporski J, Bertaina A, Zecca M, Moretta L, Locatelli F, Handgretinger R (2014) KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. Blood 124(17):2744–2747PubMedPubMedCentralCrossRef
110.
Stern M, Ruggeri L, Mancusi A, Bernardo ME, de Angelis C, Bucher C, Locatelli F, Aversa F, Velardi A (2008) Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood 112(7):2990–2995PubMedPubMedCentralCrossRef
111.
Ichinohe T, Teshima T, Matsuoka K, Maruya E, Saji H (2005) Fetal-maternal microchimerism: impact on hematopoietic stem cell transplantation. Curr Opin Immunol 17(5):546–552PubMedCrossRef
112.
113.
Handgretinger R (2012) New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol 39(6):664–673PubMedCrossRef
114.
Locatelli F, Moretta F, Brescia L, Merli P (2014) Natural killer cells in the treatment of high-risk acute leukaemia. Semin Immunol 26(2):173–179PubMedCrossRef
115.
Norell H, Moretta A, Silva-Santos B, Moretta L (2013) At the bench: preclinical rationale for exploiting NK cells and gammadelta T lymphocytes for the treatment of high-risk leukemias. J Leukoc Biol 94(6):1123–1139PubMedCrossRef
116.
Airoldi I, Bertaina A, Prigione I, Zorzoli A, Pagliara D, Cocco C, Meazza R, Loiacono F, Lucarelli B, Bernardo ME, Barbarito G, Pende D, Moretta A, Pistoia V, Moretta L, Locatelli F (2015) gammadelta T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-alphabeta +/CD19 + lymphocytes. Blood 125(15):2349–2358PubMedPubMedCentralCrossRef
117.
Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F (2014) HLA-haploidentical stem cell transplantation after removal of alphabeta + T and B cells in children with nonmalignant disorders. Blood 124(5):822–826PubMedCrossRef
Metadata
Title
Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias
Authors
Gabriella Pietra
Chiara Vitale
Daniela Pende
Alice Bertaina
Francesca Moretta
Michela Falco
Paola Vacca
Elisa Montaldo
Claudia Cantoni
Maria Cristina Mingari
Alessandro Moretta
Franco Locatelli
Lorenzo Moretta
Publication date
01-04-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 4/2016
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-015-1744-y

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