{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T23:11:53Z","timestamp":1772320313289,"version":"3.50.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The activating NK cell receptor DNAX accessory molecule-1 (DNAM-1) contributes to tumor immune surveillance and plays a crucial role in NK cell-mediated recognition of several types of human tumors, including ovarian carcinoma. Here, we have analyzed the receptor repertoire and functional integrity of NK cells in peritoneal effusions from patients with ovarian carcinoma. Relative to autologous peripheral blood NK cells, tumor-associated NK cells expressed reduced levels of the DNAM-1, 2B4, and CD16 receptors and were hyporesponsive to HLA class I-deficient K562 cells and to coactivation via DNAM-1 and 2B4. Moreover, tumor-associated NK cells were also refractory to CD16 receptor stimulation, resulting in diminished Ab-dependent cellular cytotoxicity against autologous tumor cells. Coincubation of NK cells with ovarian carcinoma cells expressing the DNAM-1 ligand CD155 led to reduction of DNAM-1 expression. Therefore, NK cell-mediated rejection of ovarian carcinoma may be limited by perturbed DNAM-1 expression on tumor-associated NK cells induced by chronic ligand exposure. Thus, these data support the notion that tumor-induced alterations of activating NK cell receptor expression may hamper immune surveillance and promote tumor progression.<\/jats:p>","DOI":"10.4049\/jimmunol.0901226","type":"journal-article","created":{"date-parts":[[2009,10,3]],"date-time":"2009-10-03T08:01:10Z","timestamp":1254556870000},"page":"4921-4930","source":"Crossref","is-referenced-by-count":237,"title":["Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells"],"prefix":"10.1093","volume":"183","author":[{"given":"Mattias","family":"Carlsten","sequence":"first","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm,","place":["Sweden"]},{"name":"Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institutet , Stockholm,","place":["Sweden"]}]},{"given":"H\u00e5kan","family":"Norell","sequence":"additional","affiliation":[{"name":"Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institutet , Stockholm,","place":["Sweden"]},{"name":"Department of Surgery, Hollings Cancer Center, Medical University of South Carolina , Charleston, SC 29425"}]},{"given":"Yenan T","family":"Bryceson","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm,","place":["Sweden"]}]},{"given":"Isabel","family":"Poschke","sequence":"additional","affiliation":[{"name":"Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institutet , Stockholm,","place":["Sweden"]}]},{"given":"Kjell","family":"Schedvins","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Karolinska University Hospital , Stockholm,","place":["Sweden"]}]},{"given":"Hans-Gustaf","family":"Ljunggren","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm,","place":["Sweden"]}]},{"given":"Rolf","family":"Kiessling","sequence":"additional","affiliation":[{"name":"Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institutet , Stockholm,","place":["Sweden"]}]},{"given":"Karl-Johan","family":"Malmberg","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm,","place":["Sweden"]}]}],"member":"286","published-online":{"date-parts":[[2009,10,15]]},"reference":[{"key":"2026012811284634400_R1","first-page":"675","article-title":"Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy.","volume-title":"Nature","year":"1986"},{"key":"2026012811284634400_R2","first-page":"3146","article-title":"Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset.","volume-title":"Blood","year":"2001"},{"key":"2026012811284634400_R3","first-page":"633","article-title":"The biology of human natural killer-cell subsets.","volume-title":"Trends Immunol.","year":"2001"},{"key":"2026012811284634400_R4","first-page":"3121","article-title":"CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells.","volume-title":"Eur. J. Immunol.","year":"2001"},{"key":"2026012811284634400_R5","first-page":"3183","article-title":"Comparative studies of human FcRIII-positive and negative natural killer cells.","volume-title":"J. Immunol.","year":"1989"},{"key":"2026012811284634400_R6","first-page":"4947","article-title":"CD56brightCD16\u2212 killer Ig-like receptor\u2212 NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811284634400_R7","first-page":"225","article-title":"NK cell recognition.","volume-title":"Annu. Rev. Immunol.","year":"2005"},{"key":"2026012811284634400_R8","first-page":"70","article-title":"Negative signaling by inhibitory receptors: the NK cell paradigm.","volume-title":"Immunol. Rev.","year":"2008"},{"key":"2026012811284634400_R9","first-page":"73","article-title":"Activation, coactivation, and costimulation of resting human natural killer cells.","volume-title":"Immunol. Rev.","year":"2006"},{"key":"2026012811284634400_R10","first-page":"159","article-title":"Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion.","volume-title":"Blood","year":"2006"},{"key":"2026012811284634400_R11","first-page":"571","article-title":"NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy.","volume-title":"Immunity","year":"2008"},{"key":"2026012811284634400_R12","first-page":"2959","article-title":"Accelerated tumor growth in mice deficient in DNAM-1 receptor.","volume-title":"J. Exp. Med.","year":"2008"},{"key":"2026012811284634400_R13","first-page":"573","article-title":"DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes.","volume-title":"Immunity","year":"1996"},{"key":"2026012811284634400_R14","first-page":"557","article-title":"Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule.","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2026012811284634400_R15","first-page":"1317","article-title":"DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells.","volume-title":"Cancer Res.","year":"2007"},{"key":"2026012811284634400_R16","first-page":"9180","article-title":"Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction.","volume-title":"Cancer Res.","year":"2004"},{"key":"2026012811284634400_R17","first-page":"8444","article-title":"The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells.","volume-title":"Cancer Res.","year":"2007"},{"key":"2026012811284634400_R18","first-page":"209","article-title":"Expression and possible role of PVR\/CD155\/Necl-5 in osteoclastogenesis.","volume-title":"Mol. Cell. Biochem.","year":"2007"},{"key":"2026012811284634400_R19","first-page":"2030","article-title":"Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction.","volume-title":"Blood","year":"2006"},{"key":"2026012811284634400_R20","first-page":"1331","article-title":"DNAM-1 and PVR regulate monocyte migration through endothelial junctions.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012811284634400_R21","first-page":"10930","article-title":"CD155\/PVR enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics.","volume-title":"Cancer Res.","year":"2005"},{"key":"2026012811284634400_R22","first-page":"6387","article-title":"Frequent loss of HLA-A2 expression in metastasizing ovarian carcinomas associated with genomic haplotype loss and HLA-A2-restricted HER-2\/neu-specific immunity.","volume-title":"Cancer Res.","year":"2006"},{"key":"2026012811284634400_R23","first-page":"67","article-title":"HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage.","volume-title":"Clin. Cancer Res.","year":"2005"},{"key":"2026012811284634400_R24","first-page":"863","article-title":"Lymphokine-activated killer activity of tumor-associated and peripheral blood lymphocytes isolated from patients with ascites ovarian tumors.","volume-title":"J. Natl. Cancer Inst.","year":"1986"},{"key":"2026012811284634400_R25","first-page":"1059","article-title":"Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL-2 stimulated NK cells of normal donors.","volume-title":"Leukemia Res.","year":"1987"},{"key":"2026012811284634400_R26","first-page":"1515","article-title":"IFN-\u03b3 protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94\/NKG2A-dependent mechanism.","volume-title":"J. Clin. Invest.","year":"2002"},{"key":"2026012811284634400_R27","first-page":"1001","article-title":"Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012811284634400_R28","first-page":"418","article-title":"Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125).","volume-title":"Immunology","year":"2007"},{"key":"2026012811284634400_R29","first-page":"3917","article-title":"NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways.","volume-title":"Mol. Immunol.","year":"2008"},{"key":"2026012811284634400_R30","first-page":"11258","article-title":"Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2006"},{"key":"2026012811284634400_R31","first-page":"1711","article-title":"Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand-expressing tumor cells.","volume-title":"Blood","year":"2005"},{"key":"2026012811284634400_R32","first-page":"15","article-title":"CD107a as a functional marker for the identification of natural killer cell activity.","volume-title":"J. Immunol. Methods","year":"2004"},{"key":"2026012811284634400_R33","first-page":"2420","article-title":"Overexpression of HER-2 in ovarian carcinomas.","volume-title":"Cancer Res.","year":"2001"},{"key":"2026012811284634400_R34","first-page":"2965","article-title":"DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors.","volume-title":"J. Exp. Med.","year":"2008"},{"key":"2026012811284634400_R35","first-page":"757","article-title":"Natural killer cell-mediated lysis of freshly isolated human tumor cells.","volume-title":"Int. J. Cancer","year":"2009"},{"key":"2026012811284634400_R36","first-page":"3661","article-title":"Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia.","volume-title":"Blood","year":"2002"},{"key":"2026012811284634400_R37","first-page":"7338","article-title":"Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012811284634400_R38","first-page":"7335","article-title":"Elevated TGF-\u03b21 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811284634400_R39","first-page":"41","article-title":"Impairment of NK cell function by NKG2D modulation in NOD mice.","volume-title":"Immunity","year":"2003"},{"key":"2026012811284634400_R40","first-page":"928","article-title":"Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance.","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2026012811284634400_R41","first-page":"3994","article-title":"Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155).","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811284634400_R42","first-page":"667","article-title":"Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage.","volume-title":"J. Exp. Med.","year":"2007"},{"key":"2026012811284634400_R43","first-page":"863","article-title":"Differential expression of KIR\/NKAT2 and CD94 molecules on decidual and peripheral blood CD56bright and CD56dim natural killer cell subsets.","volume-title":"Fertil. Steril.","year":"2004"},{"key":"2026012811284634400_R44","first-page":"3052","article-title":"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.","volume-title":"Blood","year":"2003"},{"key":"2026012811284634400_R45","first-page":"258","article-title":"Functions of human decidual NK cells.","volume-title":"Am. J. Reprod. Immunol.","year":"1996"},{"key":"2026012811284634400_R46","first-page":"119","article-title":"Preferential apoptosis of CD56dim natural killer cell subset in patients with cancer.","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026012811284634400_R47","first-page":"1199","article-title":"Human placental cytotrophoblasts attract monocytes and CD56bright natural killer cells via the actions of monocyte inflammatory protein 1\u03b1.","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026012811284634400_R48","first-page":"4513","article-title":"The CD16\u2212CD56bright NK cell subset is resistant to reactive oxygen species produced by activated granulocytes and has higher antioxidative capacity than the CD16+CD56dim subset.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811284634400_R49","first-page":"1509","article-title":"Functional consequences of interleukin 2 receptor expression on resting human lymphocytes: identification of a novel natural killer cell subset with high affinity receptors.","volume-title":"J. Exp. Med.","year":"1990"},{"key":"2026012811284634400_R50","first-page":"481","article-title":"Differential expression of the interleukin 2 receptor \u03b2 (p75) chain on human peripheral blood natural killer subsets.","volume-title":"Int. Immunol.","year":"1990"},{"key":"2026012811284634400_R51","first-page":"1217","article-title":"A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127.","volume-title":"Nat. Immunol.","year":"2006"},{"key":"2026012811284634400_R52","first-page":"704","article-title":"Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125.","volume-title":"Gynecol. Oncol.","year":"2005"},{"key":"2026012811284634400_R53","first-page":"1313","article-title":"ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15.","volume-title":"Blood","year":"2006"},{"key":"2026012811284634400_R54","first-page":"2065","article-title":"NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis.","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026012811284634400_R55","first-page":"570","article-title":"TGF\u03b2 down-regulates TLiSA1 expression and inhibits the differentiation of precursor lymphocytes into CTL and LAK cells.","volume-title":"Immunology","year":"1989"},{"key":"2026012811284634400_R56","first-page":"329","article-title":"Prospects for the use of NK cells in immunotherapy of human cancer.","volume-title":"Nat. Rev. Immunol.","year":"2007"},{"key":"2026012811284634400_R57","first-page":"e326","article-title":"Serial killing of tumor cells by human natural killer cells: enhancement by therapeutic antibodies.","volume-title":"PLoS ONE","year":"2007"},{"key":"2026012811284634400_R58","first-page":"5003","article-title":"Chimeric NKG2D receptor-bearing T cells as immunotherapy for ovarian cancer.","volume-title":"Cancer Res.","year":"2007"},{"key":"2026012811284634400_R59","first-page":"1151","article-title":"Approved monoclonal antibodies for cancer therapy.","volume-title":"Expert Opin. Biol. Ther.","year":"2008"},{"key":"2026012811284634400_R60","first-page":"161","article-title":"Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma.","volume-title":"Clin. Cancer Res.","year":"1996"},{"key":"2026012811284634400_R61","first-page":"1515","article-title":"Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients.","volume-title":"Clin. Cancer Res.","year":"2006"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/8\/4921\/62691626\/9804.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/8\/4921\/62691626\/9804.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:32:31Z","timestamp":1769617951000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/8\/4921\/8053814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2009,10,15]]},"published-print":{"date-parts":[[2009,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0901226","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,10]]},"published":{"date-parts":[[2009,10]]}}}