Top

Published in:

01-02-2017 | Focussed Research Review

Immunosenescence: limitations of natural killer cell-based cancer immunotherapy

Authors: Raquel Tarazona, Beatriz Sanchez-Correa, Ignacio Casas-Avilés, Carmen Campos, Alejandra Pera, Sara Morgado, Nelson López-Sejas, Fakhri Hassouneh, Juan M. Bergua, Maria Jose Arcos, Helena Bañas, Javier G. Casado, Esther Durán, Fernando Labella, Rafael Solana

Published in: Cancer Immunology, Immunotherapy | Issue 2/2017

Abstract

Cancer is primarily considered a disease of old age. Immunosenescence refers to the age-associated changes in the immune system, and its contribution to the increased risk of cancer in old individuals has been discussed for many years. Natural killer (NK) cells are cytotoxic innate immune cells specialized in defence against tumour and virus-infected cells. NK cell cytotoxicity is the result of a fine balance between activating and inhibitory receptors. Several activating receptors have been identified that recognize different ligands frequently found over-expressed on tumour cells or virus-infected cells. The most important NK cell inhibitory receptors interact with major histocompatibility complex class I molecules expressed on almost all nucleated cells preventing NK cell-mediated lysis of healthy cells. NK cell immunosenescence is characterized by a redistribution of NK cell subsets, a diminished expression of several activating receptors and lower per-cell cytotoxicity. Altered expression of activating receptors has also been described in young and elderly cancer patients probably due to chronic exposure to ligands on tumour cells. Thus, the effect of both age and cancer may act synergistically to diminish NK cell-mediated tumour immunosurveillance. Different strategies harnessing the power of NK cells to target tumour cells have been designed including adoptive therapy with autologous or allogeneic expanded NK cells. In addition, checkpoint blockade of inhibitory receptors and the use of agonist antibodies to stimulate activating receptors are emerging areas of research. In this context, the effect of immunosenescence should be considered to improve the efficiency of cancer immunotherapy.

Anderson AC, Joller N, Kuchroo VK (2016) Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 44:989–1004. doi:10.1016/j.immuni.2016.05.001 CrossRefPubMed

Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH (2006) Age and acute myeloid leukemia. Blood 107:3481–3485. doi:10.1182/blood-2005-09-3724 CrossRefPubMedPubMedCentral

Atsumi S, Matsumine A, Toyoda H, Niimi R, Iino T, Sudo A (2013) Prognostic significance of CD155 mRNA expression in soft tissue sarcomas. Oncol Lett 5:1771–1776. doi:10.3892/ol.2013.1280 PubMedPubMedCentral

Balducci L, Ershler WB (2005) Cancer and ageing: a nexus at several levels. Nat Rev Cancer 5:655–662. doi:10.1038/nrc1675 CrossRefPubMed

Beaulieu AM, Bezman NA, Lee JE, Matloubian M, Sun JC, Lanier LL (2013) MicroRNA function in NK-cell biology. Immunol Rev 253:40–52. doi:10.1111/imr.12045 CrossRefPubMedPubMedCentral

Benson DM Jr, Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, Baiocchi RA, Zhang J, Yu J, Smith MK, Greenfield CN, Porcu P, Devine SM, Rotem-Yehudar R, Lozanski G, Byrd JC, Caligiuri MA (2010) The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood 116:2286–2294. doi:10.1182/blood-2010-02-271874 CrossRefPubMedPubMedCentral

Benson DM Jr, Bakan CE, Zhang S, Collins SM, Liang J, Srivastava S, Hofmeister CC, Efebera Y, Andre P, Romagne F, Blery M, Bonnafous C, Zhang J, Clever D, Caligiuri MA, Farag SS (2011) IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood 118:6387–6391. doi:10.1182/blood-2011-06-360255 CrossRefPubMedPubMedCentral

Benson DM Jr, Cohen AD, Jagannath S, Munshi NC, Spitzer G, Hofmeister CC, Efebera YA, Andre P, Zerbib R, Caligiuri MA (2015) A phase I trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma. Clin Cancer Res 21:4055–4061. doi:10.1158/1078-0432.CCR-15-0304 CrossRefPubMedPubMedCentral

Boissel L, Betancur-Boissel M, Lu W, Krause DS, Van Etten RA, Wels WS, Klingemann H (2013) Retargeting NK-92 cells by means of CD19- and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity. Oncoimmunology 2:e26527. doi:10.4161/onci.26527 CrossRefPubMedPubMedCentral

10.

Bryceson YT, Long EO (2008) Line of attack: NK cell specificity and integration of signals. Curr Opin Immunol 20:344–352. doi:10.1016/j.coi.2008.03.005 CrossRefPubMedPubMedCentral

11.

Campos C, Lopez N, Pera A, Gordillo JJ, Hassouneh F, Tarazona R, Solana R (2015) Expression of NKp30, NKp46 and DNAM-1 activating receptors on resting and IL-2 activated NK cells from healthy donors according to CMV-serostatus and age. Biogerontology 16:671–683. doi:10.1007/s10522-015-9581-0 CrossRefPubMed

12.

Campos C, Pera A, Lopez-Fernandez I, Alonso C, Tarazona R, Solana R (2014) Proinflammatory status influences NK cells subsets in the elderly. Immunol Lett 162:298–302. doi:10.1016/j.imlet.2014.06.015 CrossRefPubMed

13.

Campos C, Pera A, Sanchez-Correa B, Alonso C, Lopez-Fernandez I, Morgado S, Tarazona R, Solana R (2014) Effect of age and CMV on NK cell subpopulations. Exp Gerontol 54:130–137. doi:10.1016/j.exger.2014.01.008 CrossRefPubMed

14.

Carlsten M, Bjorkstrom NK, Norell H, Bryceson Y, van Hall T, Baumann BC, Hanson M, Schedvins K, Kiessling R, Ljunggren HG, Malmberg KJ (2007) DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. Cancer Res 67:1317–1325. doi:10.1158/0008-5472.CAN-06-2264 CrossRefPubMed

15.

Casado JG, Pawelec G, Morgado S, Sanchez-Correa B, Delgado E, Gayoso I, Duran E, Solana R, Tarazona R (2009) Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines. Cancer Immunol Immunother 58:1517–1526. doi:10.1007/s00262-009-0682-y CrossRefPubMed

16.

Chiarion-Sileni V, Pigozzo J, Ascierto PA, Grimaldi AM, Maio M, Di Guardo L, Marchetti P, de Rosa F, Nuzzo C, Testori A, Cocorocchio E, Bernengo MG, Guida M, Marconcini R, Merelli B, Parmiani G, Rinaldi G, Aglietta M, Grosso M, Queirolo P (2014) Efficacy and safety of ipilimumab in elderly patients with pretreated advanced melanoma treated at Italian centres through the expanded access programme. J Exp Clin Cancer Res 33:30. doi:10.1186/1756-9966-33-30 CrossRefPubMedPubMedCentral

17.

Curti A, Ruggeri L, D’Addio A, Bontadini A, Dan E, Motta MR, Trabanelli S, Giudice V, Urbani E, Martinelli G, Paolini S, Fruet F, Isidori A, Parisi S, Bandini G, Baccarani M, Velardi A, Lemoli RM (2011) Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 118:3273–3279. doi:10.1182/blood-2011-01-329508 CrossRefPubMed

18.

Curti A, Ruggeri L, Parisi S, Bontadini A, Dan E, Motta MR, Rizzi S, Trabanelli S, Ocadlikova D, Lecciso M, Giudice V, Fruet F, Urbani E, Papayannidis C, Martinelli G, Bandini G, Bonifazi F, Lewis RE, Cavo M, Velardi A, Lemoli RM (2016) Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients. Clin Cancer Res 22:1914–1921. doi:10.1158/1078-0432.CCR-15-1604 CrossRefPubMed

19.

da Silva I, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, Osman I, Bhardwaj N (2014) Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res 2:410–422. doi:10.1158/2326-6066.CIR-13-0171 CrossRefPubMedPubMedCentral

20.

Derhovanessian E, Solana R, Larbi A, Pawelec G (2008) Immunity, ageing and cancer. Immun Ageing 5:11–15. doi:10.1186/1742-4933-5-11 CrossRefPubMedPubMedCentral

21.

Dezell SA, Ahn YO, Spanholtz J, Wang H, Weeres M, Jackson S, Cooley S, Dolstra H, Miller JS, Verneris MR (2012) Natural killer cell differentiation from hematopoietic stem cells: a comparative analysis of heparin- and stromal cell-supported methods. Biol Blood Marrow Transplant 18:536–545. doi:10.1016/j.bbmt.2011.11.023 CrossRefPubMed

22.

Eguizabal C, Zenarruzabeitia O, Monge J, Santos S, Vesga MA, Maruri N, Arrieta A, Rinon M, Tamayo-Orbegozo E, Amo L, Larrucea S, Borrego F (2014) Natural killer cells for cancer immunotherapy: pluripotent stem cells-derived NK cells as an immunotherapeutic perspective. Front Immunol 5:439. doi:10.3389/fimmu.2014.00439 CrossRefPubMedPubMedCentral

23.

Ershler WB (2005) The influence of advanced age on cancer occurrence and growth. In: Balducci L, Extermann M (eds) Biological basis of geriatric oncology. Springer, New York, pp 75–87CrossRef

24.

Fauriat C, Just-Landi S, Mallet F, Arnoulet C, Sainty D, Olive D, Costello RT (2007) Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood 109:323–330. doi:10.1182/blood-2005-08-027979 CrossRefPubMed

25.

Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB (2015) Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine. Vaccine 33:1433–1439. doi:10.1016/j.vaccine.2015.01.071 CrossRefPubMedPubMedCentral

26.

Fulop T, Larbi A, Kotb R, Pawelec G (2013) Immunology of aging and cancer development. Interdiscip Top Gerontol 38:38–48. doi:10.1159/000343599 CrossRefPubMed

27.

Furman D, Jojic V, Sharma S, Shen-Orr SS, Angel CJ, Onengut-Gumuscu S, Kidd BA, Maecker HT, Concannon P, Dekker CL, Thomas PG, Davis MM (2015) Cytomegalovirus infection enhances the immune response to influenza. Sci Transl Med 7:281ra43. doi:10.1126/scitranslmed.aaa2293 CrossRefPubMedPubMedCentral

28.

Gayoso I, Peralbo E, Sanchez-Correa B, Morgado S, Pita ML, Casado JG, Tarazona R, Solana R (2009) Phenotypic analysis of human NK cells in healthy elderly. In: Schmidt RE (ed) 2nd European congress of immunology, 1st edn. Medimond, Monduzzi Editore, Bologna, pp 105–109

29.

Gleason MK, Lenvik TR, McCullar V, Felices M, O’Brien MS, Cooley SA, Verneris MR, Cichocki F, Holman CJ, Panoskaltsis-Mortari A, Niki T, Hirashima M, Blazar BR, Miller JS (2012) Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. Blood 119:3064–3072. doi:10.1182/blood-2011-06-360321 CrossRefPubMedPubMedCentral

30.

Glienke W, Esser R, Priesner C, Suerth JD, Schambach A, Wels WS, Grez M, Kloess S, Arseniev L, Koehl U (2015) Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol 6:21. doi:10.3389/fphar.2015.00021 CrossRefPubMedPubMedCentral

31.

Grammatikakis I, Gorospe M, Abdelmohsen K (2013) Modulation of cancer traits by tumor suppressor microRNAs. Int J Mol Sci 14:1822–1842. doi:10.3390/ijms14011822 CrossRefPubMedPubMedCentral

32.

Granzin M, Soltenborn S, Muller S, Kollet J, Berg M, Cerwenka A, Childs RW, Huppert V (2015) Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy. Cytotherapy 17:621–632. doi:10.1016/j.jcyt.2015.03.611 CrossRefPubMed

33.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. doi:10.1016/j.cell.2011.02.013 CrossRefPubMed

34.

Hannier S, Tournier M, Bismuth G, Triebel F (1998) CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J Immunol 161:4058–4065PubMed

35.

Herberman RB, Nunn ME, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 16:216–229. doi:10.1002/ijc.2910160204 CrossRefPubMed

36.

Iannello A, Ahmad A (2005) Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev 24:487–499. doi:10.1007/s10555-005-6192-2 CrossRefPubMed

37.

Imai C, Iwamoto S, Campana D (2005) Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106:376–383. doi:10.1182/blood-2004-12-4797 CrossRefPubMedPubMedCentral

38.

Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4:143–159. doi:10.1002/emmm.201100209 CrossRefPubMedPubMedCentral

39.

Iwayama Y, Tsuruma T, Mizuguchi T, Furuhata T, Toyota N, Matsumura M, Torigoe T, Sato N, Hirata K (2015) Prognostic value of HLA class I expression in patients with colorectal cancer. World J Surg Oncol 13:36. doi:10.1186/s12957-015-0456-2 CrossRefPubMedPubMedCentral

40.

Kaneko K, Ishigami S, Kijima Y, Funasako Y, Hirata M, Okumura H, Shinchi H, Koriyama C, Ueno S, Yoshinaka H, Natsugoe S (2011) Clinical implication of HLA class I expression in breast cancer. BMC Cancer 11:454. doi:10.1186/1471-2407-11-454 CrossRefPubMedPubMedCentral

41.

Kiessling R, Klein E, Wigzell H (1975) “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 5:112–117. doi:10.1002/eji.1830050208 CrossRefPubMed

42.

Kim N, Kim M, Yun S, Doh J, Greenberg PD, Kim TD, Choi I (2014) MicroRNA-150 regulates the cytotoxicity of natural killers by targeting perforin-1. J Allergy Clin Immunol 134:195–203. doi:10.1016/j.jaci.2014.02.018 CrossRefPubMedPubMedCentral

43.

Korde N, Carlsten M, Lee MJ, Minter A, Tan E, Kwok M, Manasanch E, Bhutani M, Tageja N, Roschewski M, Zingone A, Costello R, Mulquin M, Zuchlinski D, Maric I, Calvo KR, Braylan R, Tembhare P, Yuan C, Stetler-Stevenson M, Trepel J, Childs R, Landgren O (2014) A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma. Haematologica 99:e81–e83. doi:10.3324/haematol.2013.103085 CrossRefPubMedPubMedCentral

44.

Lakshmikanth T, Burke S, Ali TH, Kimpfler S, Ursini F, Ruggeri L, Capanni M, Umansky V, Paschen A, Sucker A, Pende D, Groh V, Biassoni R, Hoglund P, Kato M, Shibuya K, Schadendorf D, Anichini A, Ferrone S, Velardi A, Karre K, Shibuya A, Carbone E, Colucci F (2009) 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 119:1251–1263. doi:10.1172/JCI36022 CrossRefPubMedPubMedCentral

45.

Lapteva N, Durett AG, Sun J, Rollins LA, Huye LL, Fang J, Dandekar V, Mei Z, Jackson K, Vera J, Ando J, Ngo MC, Coustan-Smith E, Campana D, Szmania S, Garg T, Moreno-Bost A, Vanrhee F, Gee AP, Rooney CM (2012) Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications. Cytotherapy 14:1131–1143. doi:10.3109/14653249.2012.700767 CrossRefPubMedPubMedCentral

46.

Lopez-Botet M, Muntasell A, Vilches C (2014) The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Semin Immunol 26:145–151. doi:10.1016/j.smim.2014.03.002 CrossRefPubMed

47.

Lopez-Verges S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, Houchins JP, Miller S, Kang SM, Norris PJ, Nixon DF, Lanier LL (2011) Expansion of a unique CD57NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci USA 108:14725–14732. doi:10.1073/pnas.1110900108 CrossRefPubMedPubMedCentral

48.

Lutz CT, Karapetyan A, Al-Attar A, Shelton BJ, Holt KJ, Tucker JH, Presnell SR (2011) Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults. J Immunol 186:4590–4598. doi:10.4049/jimmunol.1002732 CrossRefPubMedPubMedCentral

49.

Lutz CT, Moore MB, Bradley S, Shelton BJ, Lutgendorf SK (2005) Reciprocal age related change in natural killer cell receptors for MHC class I. Mech Ageing Dev 126:722–731. doi:10.1016/j.mad.2005.01.004 CrossRefPubMedPubMedCentral

50.

Mahoney KM, Rennert PD, Freeman GJ (2015) Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14:561–584. doi:10.1038/nrd4591 CrossRefPubMed

51.

Mariani E, Facchini A (2003) Characterization of NK cells in the elderly. In: Pawelec G (ed) Basic biology and clinical impact of immunosenescence, 1st edn. Elsevier Science, Amsterdam, pp 133–153

52.

Martinet L, Smyth MJ (2015) Balancing natural killer cell activation through paired receptors. Nat Rev Immunol 15:243–254. doi:10.1038/nri3799 CrossRefPubMed

53.

Michaelis M, Doerr HW, Cinatl J (2009) The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia 11:1–9. doi:10.1593/neo.81178 CrossRefPubMedPubMedCentral

54.

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 105:3051–3057. doi:10.1182/blood-2004-07-2974 CrossRefPubMed

55.

Miller JS, Warren EH, van den Brink MR, Ritz J, Shlomchik WD, Murphy WJ, Barrett AJ, Kolb HJ, Giralt S, Bishop MR, Blazar BR, Falkenburg JH (2010) NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the biology underlying recurrence of malignant disease following allogeneic HSCT: graft-versus-tumor/leukemia reaction. Biol Blood Marrow Transplant 16:565–586. doi:10.1016/j.bbmt.2010.02.005 CrossRefPubMedPubMedCentral

56.

Morgado S, Sanchez-Correa B, Casado JG, Duran E, Gayoso I, Labella F, Solana R, Tarazona R (2011) NK cell recognition and killing of melanoma cells is controlled by multiple activating receptor-ligand interactions. J Innate Immun 3:365–373. doi:10.1159/000328505 CrossRefPubMed

57.

Navabi S, Doroudchi M, Tashnizi AH, Habibagahi M (2015) Natural killer cell functional activity after 4-1BB costimulation. Inflammation 38:1181–1190. doi:10.1007/s10753-014-0082-0 CrossRefPubMed

58.

Ndhlovu LC, Lopez-Verges S, Barbour JD, Jones RB, Jha AR, Long BR, Schoeffler EC, Fujita T, Nixon DF, Lanier LL (2012) Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood 119:3734–3743. doi:10.1182/blood-2011-11-392951 CrossRefPubMedPubMedCentral

59.

Okazaki T, Okazaki IM, Wang J, Sugiura D, Nakaki F, Yoshida T, Kato Y, Fagarasan S, Muramatsu M, Eto T, Hioki K, Honjo T (2011) PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med 208:395–407. doi:10.1084/jem.20100466 CrossRefPubMedPubMedCentral

60.

Patel SS, Nelson R, Sanchez J, Lee W, Uyeno L, Garcia-Aguilar J, Hurria A, Kim J (2013) Elderly patients with colon cancer have unique tumor characteristics and poor survival. Cancer 119:739–747. doi:10.1002/cncr.27753 CrossRefPubMed

61.

Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E (2012) The impact of CMV infection on survival in older humans. Curr Opin Immunol 24:507–511. doi:10.1016/j.coi.2012.04.002 CrossRefPubMed

62.

Pera A, Campos C, Corona A, Sanchez-Correa B, Tarazona R, Larbi A, Solana R (2014) CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals. PLoS ONE 9:e88538. doi:10.1371/journal.pone.0088538 CrossRefPubMedPubMedCentral

63.

Perez-Gracia JL, Labiano S, Rodriguez-Ruiz ME, Sanmamed MF, Melero I (2014) Orchestrating immune check-point blockade for cancer immunotherapy in combinations. Curr Opin Immunol 27:89–97. doi:10.1016/j.coi.2014.01.002 CrossRefPubMed

64.

Poschke I, De BJ, Mao Y, Kiessling R (2012) Tumor-induced changes in the phenotype of blood-derived and tumor-associated T cells of early stage breast cancer patients. Int J Cancer 131:1611–1620. doi:10.1002/ijc.27410 CrossRefPubMed

65.

Raulet DH, Gasser S, Gowen BG, Deng W, Jung H (2013) Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol 31:413–441. doi:10.1146/annurev-immunol-032712-095951 CrossRefPubMedPubMedCentral

66.

Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532. doi:10.1056/NEJMoa1503093 CrossRefPubMed

67.

Romagne F, Andre P, Spee P, Zahn S, Anfossi N, Gauthier L, Capanni M, Ruggeri L, Benson DM Jr, Blaser BW, Della CM, 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 114:2667–2677. doi:10.1182/blood-2009-02-206532 CrossRefPubMedPubMedCentral

68.

Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris M, Walcheck B, Miller J (2013) NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood 121:3599–3608. doi:10.1182/blood-2012-04-425397 CrossRefPubMedPubMedCentral

69.

Romee R, Leong JW, Fehniger TA (2014) Utilizing cytokines to function-enable human NK cells for the immunotherapy of cancer. Scientifica 2014:205796. doi:10.1155/2014/205796 CrossRefPubMedPubMedCentral

70.

Ruggeri L, Mancusi A, Burchielli E, Capanni M, Carotti A, Aloisi T, Aversa F, Martelli MF, Velardi A (2008) NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. Blood Cells Mol Dis 40:84–90. doi:10.1016/j.bcmd.2007.06.029 CrossRefPubMed

71.

Rusakiewicz S, Semeraro M, Sarabi M, Desbois M, Locher C, Mendez R, Vimond N, Concha A, Garrido F, Isambert N, Chaigneau L, Le Brun-Ly V, Dubreuil P, Cremer I, Caignard A, Poirier-Colame V, Chaba K, Flament C, Halama N, Jager D, Eggermont A, Bonvalot S, Commo F, Terrier P, Opolon P, Emile JF, Coindre JM, Kroemer G, Chaput N, Le CA, Blay JY, Zitvogel L (2013) Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res 73:3499–3510. doi:10.1158/0008-5472.CAN-13-0371 CrossRefPubMed

72.

Sanchez-Correa B, Campos C, Pera A, Bergua JM, Arcos MJ, Banas H, Casado JG, Morgado S, Duran E, Solana R, Tarazona R (2016) Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies? Cancer Immunol Immunother 65:453–463. doi:10.1007/s00262-015-1720-6 CrossRefPubMed

73.

Sanchez-Correa B, Gayoso I, Bergua JM, Casado JG, Morgado S, Solana R, Tarazona R (2012) Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol Cell Biol 90:109–115. doi:10.1038/icb.2011.15 CrossRefPubMed

74.

Sanchez-Correa B, Morgado S, Gayoso I, Bergua JM, Casado JG, Arcos MJ, Bengochea ML, Duran E, Solana R, Tarazona R (2011) Human NK cells in acute myeloid leukaemia patients: analysis of NK cell-activating receptors and their ligands. Cancer Immunol Immunother 60:1195–1205. doi:10.1007/s00262-011-1050-2 CrossRefPubMed

75.

Schonfeld K, Sahm C, Zhang C, Naundorf S, Brendel C, Odendahl M, Nowakowska P, Bonig H, Kohl U, Kloess S, Kohler S, Holtgreve-Grez H, Jauch A, Schmidt M, Schubert R, Kuhlcke K, Seifried E, Klingemann HG, Rieger MA, Tonn T, Grez M, Wels WS (2015) Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther 23:330–338. doi:10.1038/mt.2014.219 CrossRefPubMed

76.

Segal NH, Gopal AK, Bhatia S, Kohrt HE, Levy R, Pishvaian MJ, Houot R, Bartlett N, Nghiem P, Kronenberg SA, Thall AD, Mugundu G, Huang B, Davis C (2014) A phase 1 study of PF-05082566 (anti-4-1BB) in patients with advanced cancer. J Clin Oncol 32:3007 (abstract)

77.

Solana R, Campos C, Pera A, Tarazona R (2014) Shaping of NK cell subsets by aging. Curr Opin Immunol 29:56–61. doi:10.1016/j.coi.2014.04.002 CrossRefPubMed

78.

Solana R, Mariani E (2000) NK and NK/T cells in human senescence. Vaccine 18:1613–1620. doi:10.1016/S0264-410X(99)00495-8 CrossRefPubMed

79.

Suck G, Odendahl M, Nowakowska P, Seidl C, Wels WS, Klingemann HG, Tonn T (2016) NK-92: an ‘off-the-shelf therapeutic’ for adoptive natural killer cell-based cancer immunotherapy. Cancer Immunol Immunother 65:485–492. doi:10.1007/s00262-015-1761-x CrossRefPubMed

80.

Sullivan RP, Leong JW, Fehniger TA (2013) MicroRNA regulation of natural killer cells. Front Immunol 4:44. doi:10.3389/fimmu.2013.00044 CrossRefPubMedPubMedCentral

81.

Talarico L, Chen G, Pazdur R (2004) Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 22:4626–4631. doi:10.1200/JCO.2004.02.175 CrossRefPubMed

82.

Tarazona R, Duran E, Solana R (2016) Natural killer cell recognition of melanoma: new clues for a more effective immunotherapy. Front Immunol 6:649. doi:10.3389/fimmu.2015.00649 CrossRefPubMedPubMedCentral

83.

Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T (1990) LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med 171:1393–1405CrossRefPubMed

84.

Waldhauer I, Steinle A (2008) NK cells and cancer immunosurveillance. Oncogene 27:5932–5943. doi:10.1038/onc.2008.267 CrossRefPubMed

85.

Xu F, Liu J, Liu D, Liu B, Wang M, Hu Z, Du X, Tang L, He F (2014) LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses. Cancer Res 74:3418–3428. doi:10.1158/0008-5472.CAN-13-2690 CrossRefPubMed

86.

Yakabe K, Murakami A, Nishimoto Y, Kajimura T, Sueoka K, Sugino N (2015) Clinical implications of human leukocyte antigen class I expression in endometrial cancer. Mol Clin Oncol 3:1285–1290. doi:10.3892/mco.2015.636 PubMedPubMedCentral

87.

Zamai L, Ponti C, Mirandola P, Gobbi G, Papa S, Galeotti L, Cocco L, Vitale M (2007) NK cells and cancer. J Immunol 178:4011–4016. doi:10.4049/jimmunol.178.7.4011 CrossRefPubMed

88.

Zhang C, Burger MC, Jennewein L, Genssler S, Schonfeld K, Zeiner P, Hattingen E, Harter PN, Mittelbronn M, Tonn T, Steinbach JP, Wels WS (2015) ErbB2/HER2-specific NK cells for targeted therapy of glioblastoma. J Natl Cancer Inst. doi:10.1093/jnci/djv375

89.

Zhang G, Liu R, Zhu X, Wang L, Ma J, Han H, Wang X, Zhang G, He W, Wang W, Liu C, Li S, Sun M, Gao B (2013) Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody. Immunol Cell Biol 91:615–624. doi:10.1038/icb.2013.45 CrossRefPubMed

90.

Zhou Q, Gil-Krzewska A, Peruzzi G, Borrego F (2013) Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy. Clin Exp Immunol 173:131–139. doi:10.1111/cei.12095 CrossRefPubMedPubMedCentral

Title: Immunosenescence: limitations of natural killer cell-based cancer immunotherapy
Authors: Raquel Tarazona
Beatriz Sanchez-Correa
Ignacio Casas-Avilés
Carmen Campos
Alejandra Pera
Sara Morgado
Nelson López-Sejas
Fakhri Hassouneh
Juan M. Bergua
Maria Jose Arcos
Helena Bañas
Javier G. Casado
Esther Durán
Fernando Labella
Rafael Solana
Publication date: 01-02-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 2/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1882-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

Interleukin 10 expression is related to aggressiveness and poor prognosis of patients with thyroid cancer

Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies

Using natural products to promote caspase-8-dependent cancer cell death

Immunotherapy after hematopoietic stem cell transplantation using umbilical cord blood-derived products

Cytokine-induced killer cells hunt individual cancer cells in droves in a mouse model

Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon

Keynote webinar | Spotlight on antibody–drug conjugates in cancer