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.

@article{citeulike:1455570, abstract = {NK cells are able to discriminate between normal cells and cells that have lost MHC class I (MHC-I) molecule expression as a result of tumor transformation. 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 beta2-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- 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.}, address = {Laboratoire Cytokines et Immunologie des Tumeurs humaines, U487 Institut National de la Sant\'{e} et de la Recherche M\'{e}dicale, Villejuif, France.}, author = {Le Maux Chansac, B. and Moretta, A. and Vergnon, I. and Opolon, P. and L\'{e}cluse, Y. and Grunenwald, D. and Kubin, M. and Soria, J. C. and Chouaib, S. and Mami-Chouaib, F. }, citeulike-article-id = {1455570}, issn = {0022-1767}, journal = {J Immunol}, keywords = {expression, ligands, nkg2d, selection, tumor}, month = {November}, number = {9}, pages = {5790--5798}, posted-at = {2007-07-14 02:36:36}, priority = {2}, 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.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16237071}, volume = {175}, year = {2005} }

TY - JOUR ID - citeulike:1455570 L3 - citeulike-article-id:1455570 TI - 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. JF - J Immunol VL - 175 IS - 9 SP - 5790 EP - 5798 AD - Laboratoire Cytokines et Immunologie des Tumeurs humaines, U487 Institut National de la Santé et de la Recherche Médicale, Villejuif, France. SN - 0022-1767 N2 - NK cells are able to discriminate between normal cells and cells that have lost MHC class I (MHC-I) molecule expression as a result of tumor transformation. 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 beta2-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- 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. KW - expression KW - ligands KW - nkg2d KW - selection KW - tumor AU - Le Maux Chansac, B AU - Moretta, A AU - Vergnon, I AU - Opolon, P AU - Lécluse, Y AU - Grunenwald, D AU - Kubin, M AU - Soria, JC AU - Chouaib, S AU - Mami-Chouaib, F PY - 2005/11/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/16237071 ER -