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This function is the outcome of the capacity of inhibitory NK receptors to block cytotoxicity upon interaction with their MHC-I ligands expressed on target cells. To investigate the role of human NK cells and their various receptors in the control of MHC-I-deficient tumors, we have isolated several NK cell clones from lymphocytes infiltrating an adenocarcinoma lacking \u03b22-microglobulin expression. Unexpectedly, although these clones expressed NKG2D and mediated a strong cytolytic activity toward K562, Daudi and allogeneic MHC-class I+ carcinoma cells, they were unable to lyse the autologous MHC-I\u2212 tumor cell line. This defect was associated with alterations in the expression of natural cytotoxicity receptor (NCR) by NK cells and the NKG2D ligands, MHC-I-related chain A, MHC-I-related chain B, and UL16 binding protein 1, and the ICAM-1 by tumor cells. In contrast, the carcinoma cell line was partially sensitive to allogeneic healthy donor NK cells expressing high levels of NCR. Indeed, this lysis was inhibited by anti-NCR and anti-NKG2D mAbs, suggesting that both receptors are required for the induced killing. The present study indicates that the MHC-I-deficient lung adenocarcinoma had developed mechanisms of escape from the innate immune response based on down-regulation of NCR and ligands required for target cell recognition.<\/jats:p>","DOI":"10.4049\/jimmunol.175.9.5790","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:54:18Z","timestamp":1398034458000},"page":"5790-5798","source":"Crossref","is-referenced-by-count":77,"title":["NK Cells Infiltrating a MHC Class I-Deficient Lung Adenocarcinoma Display Impaired Cytotoxic Activity toward Autologous Tumor Cells Associated with Altered NK Cell-Triggering Receptors"],"prefix":"10.1093","volume":"175","author":[{"given":"Be\u0301atrice","family":"Le Maux Chansac","sequence":"first","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs humaines, U487 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Moretta","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Sezione di Istologia and Centro di Eccellenza per le Ricerche Biomediche, Universita\u0300 di Genova , Genova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Vergnon","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs humaines, U487 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paule","family":"Opolon","sequence":"additional","affiliation":[{"name":"Unite\u0301 mixte de Recherche 8121, Centre national de la Recherche scientifique (CNRS) , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Le\u0301cluse","sequence":"additional","affiliation":[{"name":"Unite\u0301 Mixte de Recherche 8126, CNRS , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Grunenwald","sequence":"additional","affiliation":[{"name":"De\u0301partement de Chirurgie thoracique, Institut Montsouris , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kubin","sequence":"additional","affiliation":[{"name":"Amgen , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Soria","sequence":"additional","affiliation":[{"name":"De\u0301partement de Me\u0301decine, Institut Gustave Roussy , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Chouaib","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs humaines, U487 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathia","family":"Mami-Chouaib","sequence":"additional","affiliation":[{"name":"Laboratoire Cytokines et Immunologie des Tumeurs humaines, U487 Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale , Villejuif ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,11,1]]},"reference":[{"key":"2026020212165892900_R1","first-page":"6","volume-title":"Nat. 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