{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:34:04Z","timestamp":1792791244946,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome <jats:italic>in vivo<\/jats:italic> remains unknown. Here, we show that WASp KO NK cells had decreased capacity to degranulate and produce IFN\u03b3 upon NKp46 stimulation and this was associated with reduced capacity to kill MHC class I-deficient hematopoietic grafts. Pre-treatment of WASp KO NK cells with IL-2 <jats:italic>ex vivo<\/jats:italic> restored degranulation, IFN\u03b3 production and killing of MHC class I negative hematopoietic grafts. Moreover, WASp KO mice controlled growth of A20 lymphoma cells that naturally produced IL-2. WASp KO NK cells showed increased expression of DNAM-1, LAG-3 and KLRG1, all receptors associated with cellular exhaustion and NK cell memory. NK cells isolated from WAS patient spleen cells showed increased expression of DNAM-1 and had low to negative expression of CD56, a phenotype associated with NK cells exhaustion. Finally, in a cohort of neuroblastoma patients we identified a strong correlation between WASp, IL-2 and patient survival.<\/jats:p>","DOI":"10.1038\/srep30636","type":"journal-article","created":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T10:00:48Z","timestamp":1470045648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo"],"prefix":"10.1038","volume":"6","author":[{"given":"Joanna S.","family":"Kritikou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carin I. M.","family":"Dahlberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa A. P.","family":"Baptista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnika K.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki P.","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavesh Amar","family":"Gwalani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeepta K.","family":"Panda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klas","family":"K\u00e4rre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Kaech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Wermeling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan S.","family":"Orange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Brauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa S.","family":"Westerberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,1]]},"reference":[{"key":"BFsrep30636_CR1","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/nri1863","volume":"6","author":"DH Raulet","year":"2006","unstructured":"Raulet, D. H. & Vance, R. E. Self-tolerance of natural killer cells. Nat Rev Immunol 6, 520\u2013531 (2006).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep30636_CR2","doi-asserted-by":"publisher","first-page":"6565","DOI":"10.4049\/jimmunol.174.11.6565","volume":"174","author":"LL Lanier","year":"2005","unstructured":"Lanier, L. L. Missing self, NK cells and The White Album. J Immunol 174, 6565 (2005).","journal-title":"J Immunol"},{"key":"BFsrep30636_CR3","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/nri3174","volume":"12","author":"E Vivier","year":"2012","unstructured":"Vivier, E., Ugolini, S., Blaise, D., Chabannon, C. & Brossay, L. Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 12, 239\u2013252 (2012).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep30636_CR4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nri3370","volume":"13","author":"P Parham","year":"2013","unstructured":"Parham, P. & Moffett, A. Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution. Nat Rev Immunol 13, 133\u2013144 (2013).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep30636_CR5","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nri3044","volume":"11","author":"JC Sun","year":"2011","unstructured":"Sun, J. C. & Lanier, L. L. NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat Rev Immunol 11, 645\u2013657 (2011).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep30636_CR6","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/319675a0","volume":"319","author":"K Karre","year":"1986","unstructured":"Karre, K., Ljunggren, H. G., Piontek, G. & Kiessling, R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675\u2013678 (1986).","journal-title":"Nature"},{"key":"BFsrep30636_CR7","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1182\/blood-2008-05-156836","volume":"113","author":"P Brodin","year":"2009","unstructured":"Brodin, P., Lakshmikanth, T., Johansson, S., Karre, K. & Hoglund, P. The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells. Blood 113, 2434\u20132441 (2009).","journal-title":"Blood"},{"key":"BFsrep30636_CR8","doi-asserted-by":"publisher","first-page":"4416","DOI":"10.1182\/blood-2004-08-3156","volume":"105","author":"NC Fernandez","year":"2005","unstructured":"Fernandez, N. C. et al. A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105, 4416\u20134423 (2005).","journal-title":"Blood"},{"key":"BFsrep30636_CR9","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nature03847","volume":"436","author":"S Kim","year":"2005","unstructured":"Kim, S. et al. Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436, 709\u2013713 (2005).","journal-title":"Nature"},{"key":"BFsrep30636_CR10","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nri3862","volume":"15","author":"EJ Wherry","year":"2015","unstructured":"Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 15, 486\u2013499 (2015).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep30636_CR11","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1172\/JCI31184","volume":"117","author":"JF Grosso","year":"2007","unstructured":"Grosso, J. F. et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest 117, 3383\u20133392 (2007).","journal-title":"J Clin Invest"},{"key":"BFsrep30636_CR12","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.immuni.2009.04.019","volume":"31","author":"Y Li","year":"2009","unstructured":"Li, Y. et al. Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity 31, 35\u201346 (2009).","journal-title":"Immunity"},{"key":"BFsrep30636_CR13","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1002\/eji.201040506","volume":"40","author":"S Jonjic","year":"2010","unstructured":"Jonjic, S. Functional plasticity and robustness are essential characteristics of biological systems: lessons learned from KLRG1-deficient mice. Eur J Immunol 40, 1241\u20131243 (2010).","journal-title":"Eur J Immunol"},{"key":"BFsrep30636_CR14","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.4049\/jimmunol.1300876","volume":"192","author":"M Malaise","year":"2014","unstructured":"Malaise, M. et al. KLRG1+ NK cells protect T-bet-deficient mice from pulmonary metastatic colorectal carcinoma. J Immunol 192, 1954\u20131961 (2014).","journal-title":"J Immunol"},{"key":"BFsrep30636_CR15","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/imr.12107","volume":"256","author":"K Lagrue","year":"2013","unstructured":"Lagrue, K. et al. The central role of the cytoskeleton in mechanisms and functions of the NK cell immune synapse. Immunol Rev 256, 203\u2013221 (2013).","journal-title":"Immunol Rev"},{"key":"BFsrep30636_CR16","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.4049\/jimmunol.174.5.2602","volume":"174","author":"W Huang","year":"2005","unstructured":"Huang, W., Ochs, H. D., Dupont, B. & Vyas, Y. M. The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-kappa B (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangement. J Immunol 174, 2602\u20132611 (2005).","journal-title":"J Immunol"},{"key":"BFsrep30636_CR17","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1172\/JCI44862","volume":"121","author":"JS Orange","year":"2011","unstructured":"Orange, J. S. et al. IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function. J Clin Invest 121, 1535\u20131548, (2011).","journal-title":"J Clin Invest"},{"key":"BFsrep30636_CR18","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/s12288-014-0377-1","volume":"30","author":"J Senapati","year":"2014","unstructured":"Senapati, J. et al. Diffuse large B cell lymphoma in wiskott-Aldrich syndrome: a case report and review of literature. Indian journal of hematology & blood transfusion: an official journal of Indian Society of Hematology and Blood Transfusion 30, 309\u2013313 (2014).","journal-title":"Indian journal of hematology & blood transfusion: an official journal of Indian Society of Hematology and Blood Transfusion"},{"key":"BFsrep30636_CR19","doi-asserted-by":"publisher","first-page":"64","DOI":"10.2350\/10-01-0787-CR.1","volume":"14","author":"S Du","year":"2011","unstructured":"Du, S. et al. Hodgkin\u2019s and non-Hodgkin\u2019s lymphomas occurring in two brothers with Wiskott-Aldrich syndrome and review of the literature. Pediatric and developmental pathology: the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 14, 64\u201370 (2011).","journal-title":"Pediatric and developmental pathology: the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society"},{"key":"BFsrep30636_CR20","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/S0022-3476(05)82002-5","volume":"125","author":"KE Sullivan","year":"1994","unstructured":"Sullivan, K. E., Mullen, C. A., Blaese, R. M. & Winkelstein, J. A. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr 125, 876\u2013885 (1994).","journal-title":"J Pediatr"},{"key":"BFsrep30636_CR21","first-page":"5465s","volume":"52","author":"AH Filipovich","year":"1992","unstructured":"Filipovich, A. H., Mathur, A., Kamat, D. & Shapiro, R. S. Primary immunodeficiencies: genetic risk factors for lymphoma. Cancer Res 52, 5465s\u20135467s (1992).","journal-title":"Cancer Res"},{"key":"BFsrep30636_CR22","first-page":"1263","volume":"28","author":"K Salavoura","year":"2008","unstructured":"Salavoura, K., Kolialexi, A., Tsangaris, G. & Mavrou, A. Development of cancer in patients with primary immunodeficiencies. Anticancer Res 28, 1263\u20131269 (2008).","journal-title":"Anticancer Res"},{"key":"BFsrep30636_CR23","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/eji.201343935","volume":"44","author":"M Catucci","year":"2014","unstructured":"Catucci, M. et al. Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity. Eur J Immunol 44, 1039\u20131045 (2014).","journal-title":"Eur J Immunol"},{"key":"BFsrep30636_CR24","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.celrep.2013.07.007","volume":"4","author":"D Ishihara","year":"2013","unstructured":"Ishihara, D. et al. Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis. Cell reports 4, 429\u2013436 (2013).","journal-title":"Cell reports"},{"key":"BFsrep30636_CR25","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1182\/blood-2003-07-2621","volume":"104","author":"A Gismondi","year":"2004","unstructured":"Gismondi, A. et al. Impaired natural and CD16-mediated NK cell cytotoxicity in patients with WAS and XLT: ability of IL-2 to correct NK cell functional defect. Blood 104, 436\u2013443 (2004).","journal-title":"Blood"},{"key":"BFsrep30636_CR26","doi-asserted-by":"publisher","first-page":"5439","DOI":"10.1182\/blood-2011-04-348912","volume":"118","author":"JW Fathman","year":"2011","unstructured":"Fathman, J. W. et al. Identification of the earliest natural killer cell-committed progenitor in murine bone marrow. Blood 118, 5439\u20135447 (2011).","journal-title":"Blood"},{"key":"BFsrep30636_CR27","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1084\/jem.20050167","volume":"201","author":"S Johansson","year":"2005","unstructured":"Johansson, S. et al. Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules. J Exp Med 201, 1145\u20131155 (2005).","journal-title":"J Exp Med"},{"key":"BFsrep30636_CR28","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1084\/jem.20030958","volume":"198","author":"K Shibuya","year":"2003","unstructured":"Shibuya, K. et al. CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med 198, 1829\u20131839 (2003).","journal-title":"J Exp Med"},{"key":"BFsrep30636_CR29","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.immuni.2011.11.016","volume":"36","author":"SM Gordon","year":"2012","unstructured":"Gordon, S. M. et al. The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity 36, 55\u201367 (2012).","journal-title":"Immunity"},{"key":"BFsrep30636_CR30","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.immuni.2015.05.023","volume":"42","author":"V Kalia","year":"2015","unstructured":"Kalia, V., Penny, L. A., Yuzefpolskiy, Y., Baumann, F. M. & Sarkar, S. Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4. Immunity 42, 1116\u20131129 (2015).","journal-title":"Immunity"},{"key":"BFsrep30636_CR31","doi-asserted-by":"publisher","first-page":"11351","DOI":"10.1073\/pnas.162376099","volume":"99","author":"JS Orange","year":"2002","unstructured":"Orange, J. S. et al. Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses. Proc Natl Acad Sci USA 99, 11351\u201311356 (2002).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep30636_CR32","doi-asserted-by":"publisher","first-page":"9180","DOI":"10.1158\/0008-5472.CAN-04-2682","volume":"64","author":"R Castriconi","year":"2004","unstructured":"Castriconi, R. et al. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer Res 64, 9180\u20139184 (2004).","journal-title":"Cancer Res"},{"key":"BFsrep30636_CR33","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.coi.2010.09.008","volume":"23","author":"Y Ma","year":"2011","unstructured":"Ma, Y., Aymeric, L., Locher, C., Kroemer, G. & Zitvogel, L. The dendritic cell-tumor cross-talk in cancer. Curr Opin Immunol 23, 146\u2013152 (2011).","journal-title":"Curr Opin Immunol"},{"key":"BFsrep30636_CR34","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/j.jaci.2008.10.023","volume":"122","author":"E Ozcan","year":"2008","unstructured":"Ozcan, E., Notarangelo, L. D. & Geha, R. S. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol 122, 1054\u20131062 (2008).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep30636_CR35","doi-asserted-by":"publisher","first-page":"ra21","DOI":"10.1126\/scisignal.2001608","volume":"4","author":"S Guia","year":"2011","unstructured":"Guia, S. et al. Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance. Sci Signal 4, ra21 (2011).","journal-title":"Sci Signal"},{"key":"BFsrep30636_CR36","doi-asserted-by":"publisher","first-page":"ra62","DOI":"10.1126\/scisignal.2003947","volume":"6","author":"SV Pageon","year":"2013","unstructured":"Pageon, S. V. et al. Superresolution microscopy reveals nanometer-scale reorganization of inhibitory natural killer cell receptors upon activation of NKG2D. Sci Signal 6, ra62 (2013).","journal-title":"Sci Signal"},{"key":"BFsrep30636_CR37","doi-asserted-by":"publisher","first-page":"15424","DOI":"10.1073\/pnas.0706881104","volume":"104","author":"V Cotta-de-Almeida","year":"2007","unstructured":"Cotta-de-Almeida, V. et al. Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proc Natl Acad Sci USA 104, 15424\u201315429 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep30636_CR38","doi-asserted-by":"publisher","first-page":"3966","DOI":"10.1182\/blood-2010-09-308197","volume":"119","author":"LS Westerberg","year":"2012","unstructured":"Westerberg, L. S. et al. Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function. Blood 119, 3966\u20133974 (2012).","journal-title":"Blood"},{"key":"BFsrep30636_CR39","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.it.2010.08.003","volume":"31","author":"NK Bjorkstrom","year":"2010","unstructured":"Bjorkstrom, N. K., Ljunggren, H. G. & Sandberg, J. K. CD56 negative NK cells: origin, function and role in chronic viral disease. Trends in immunology 31, 401\u2013406 (2010).","journal-title":"Trends in immunology"},{"key":"BFsrep30636_CR40","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.immuni.2013.12.011","volume":"40","author":"T Nabekura","year":"2014","unstructured":"Nabekura, T. et al. Costimulatory molecule DNAM-1 is essential for optimal differentiation of memory natural killer cells during mouse cytomegalovirus infection. Immunity 40, 225\u2013234 (2014).","journal-title":"Immunity"},{"key":"BFsrep30636_CR41","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.celrep.2015.03.006","volume":"11","author":"L Martinet","year":"2015","unstructured":"Martinet, L. et al. DNAM-1 expression marks an alternative program of NK cell maturation. Cell reports 11, 85\u201397 (2015).","journal-title":"Cell reports"},{"key":"BFsrep30636_CR42","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1189\/jlb.1208745","volume":"86","author":"S Seth","year":"2009","unstructured":"Seth, S. et al. Heterogeneous expression of the adhesion receptor CD226 on murine NK and T cells and its function in NK-mediated killing of immature dendritic cells. J Leukoc Biol 86, 91\u2013101 (2009).","journal-title":"J Leukoc Biol"},{"key":"BFsrep30636_CR43","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1084\/jem.20030788","volume":"198","author":"C Bottino","year":"2003","unstructured":"Bottino, C. et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med 198, 557\u2013567 (2003).","journal-title":"J Exp Med"},{"key":"BFsrep30636_CR44","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.immuni.2007.07.010","volume":"27","author":"NS Joshi","year":"2007","unstructured":"Joshi, N. S. et al. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27, 281\u2013295 (2007).","journal-title":"Immunity"},{"key":"BFsrep30636_CR45","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nature10975","volume":"484","author":"AM Levin","year":"2012","unstructured":"Levin, A. M. et al. Exploiting a natural conformational switch to engineer an interleukin-2 \u2018superkine\u2019. Nature 484, 529\u2013533 (2012).","journal-title":"Nature"},{"key":"BFsrep30636_CR46","doi-asserted-by":"publisher","first-page":"4781","DOI":"10.1172\/JCI74337","volume":"124","author":"M Ardolino","year":"2014","unstructured":"Ardolino, M. et al. Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. J Clin Invest 124, 4781\u20134794 (2014).","journal-title":"J Clin Invest"},{"key":"BFsrep30636_CR47","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1084\/jem.20100570","volume":"207","author":"NT Joncker","year":"2010","unstructured":"Joncker, N. T., Shifrin, N., Delebecque, F. & Raulet, D. H. Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment. J Exp Med 207, 2065\u20132072 (2010).","journal-title":"J Exp Med"},{"key":"BFsrep30636_CR48","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1158\/2326-6066.CIR-15-0001","volume":"4","author":"AK Wagner","year":"2016","unstructured":"Wagner, A. K. et al. Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response. Cancer immunology research 4, 113\u2013123 (2016).","journal-title":"Cancer immunology research"},{"key":"BFsrep30636_CR49","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s12016-009-8131-4","volume":"38","author":"S Roy-Ghanta","year":"2010","unstructured":"Roy-Ghanta, S. & Orange, J. S. Use of cytokine therapy in primary immunodeficiency. Clin Rev Allergy Immunol 38, 39\u201353 (2010).","journal-title":"Clin Rev Allergy Immunol"},{"key":"BFsrep30636_CR50","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.coi.2015.11.001","volume":"38","author":"A Iannello","year":"2016","unstructured":"Iannello, A., Thompson, T. W., Ardolino, M., Marcus, A. & Raulet, D. H. Immunosurveillance and immunotherapy of tumors by innate immune cells. Curr Opin Immunol 38, 52\u201358 (2016).","journal-title":"Curr Opin Immunol"},{"key":"BFsrep30636_CR51","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.1365-2796.2009.02121.x","volume":"266","author":"T Sutlu","year":"2009","unstructured":"Sutlu, T. & Alici, E. Natural killer cell-based immunotherapy in cancer: current insights and future prospects. Journal of internal medicine 266, 154\u2013181 (2009).","journal-title":"Journal of internal medicine"},{"key":"BFsrep30636_CR52","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.4049\/jimmunol.175.2.1329","volume":"175","author":"MI Lutskiy","year":"2005","unstructured":"Lutskiy, M. I., Rosen, F. S. & Remold-O\u2019Donnell, E. Genotype-proteotype linkage in the Wiskott-Aldrich syndrome. J Immunol 175, 1329\u20131336 (2005).","journal-title":"J Immunol"},{"key":"BFsrep30636_CR53","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.4049\/jimmunol.1300960","volume":"192","author":"SL Wickstrom","year":"2014","unstructured":"Wickstrom, S. L., Oberg, L., Karre, K. & Johansson, M. H. A genetic defect in mice that impairs missing self recognition despite evidence for normal maturation and MHC class I-dependent education of NK cells. J Immunol 192, 1577\u20131586 (2014).","journal-title":"J Immunol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep30636","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep30636.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep30636.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T21:40:19Z","timestamp":1672868419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep30636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,1]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,11,14]]}},"alternative-id":["BFsrep30636"],"URL":"https:\/\/doi.org\/10.1038\/srep30636","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,1]]},"assertion":[{"value":"1 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"30636"}}