TY - JOUR
T1 - Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma
T2 - Role of NKG2D-dependent pathway
AU - Le Maux Chansac, Béatrice
AU - Missé, Dorothée
AU - Richon, Catherine
AU - Vergnon, Isabelle
AU - Kubin, Marek
AU - Soria, Jean Charles
AU - Moretta, Alessandro
AU - Chouaib, Salem
AU - Mami-Chouaib, Fathia
N1 - Funding Information:
This work was part funded by EPSRC, and the International Collaborative Energy Technology R&D Program of the Korean Institute of Energy Technology Evaluation and Planning (KETEP) with financial resource from the Ministry of Trade, Industry & Energy, Republic of Korea (no. 20148520011250). J. T.-W. W. acknowledges Swire Educational Trust for supporting his DPhil study at Oxford, and thanks Will Y.-K. Peng, and the members in the HJS and RJN group for helpful discussion. W. Z. thanks the Supergen super solar project for funding support. R. Z. thanks Prof. Bing Shen, Mr Haoran Ma and Xianguo Lang from the School of Earth and Space Sciences at Peking University for help in the ICP-OES analysis.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human non-small-cell lung carcinoma cell lines, and we analyzed their role in tumor cell susceptibility to NK cell lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels of NKG2DLs, they were often resistant to NK cell-mediated killing. Resistance of a selected cell line, ADC-Coco, to allogeneic polyclonal NK cells and autologous NK cell clones correlated with shedding of NKG2DLs resulting from a matrix metalloproteinase (MMP) production. Treatment of ADC-Coco cells with a MMP inhibitor (MMPI) combined with IL-15 stimulation of autologous NK cell clones lead to a potentiation of NK cell-mediated cytotoxicity. This lysis is mainly NKG2D mediated, since it is abrogated by anti-NKG2D-neutralizing mAb. These results suggest that MMPIs, in combination with IL-15, may be useful for overcoming tumor cell escape from the innate immune response.
AB - Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human non-small-cell lung carcinoma cell lines, and we analyzed their role in tumor cell susceptibility to NK cell lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels of NKG2DLs, they were often resistant to NK cell-mediated killing. Resistance of a selected cell line, ADC-Coco, to allogeneic polyclonal NK cells and autologous NK cell clones correlated with shedding of NKG2DLs resulting from a matrix metalloproteinase (MMP) production. Treatment of ADC-Coco cells with a MMP inhibitor (MMPI) combined with IL-15 stimulation of autologous NK cell clones lead to a potentiation of NK cell-mediated cytotoxicity. This lysis is mainly NKG2D mediated, since it is abrogated by anti-NKG2D-neutralizing mAb. These results suggest that MMPIs, in combination with IL-15, may be useful for overcoming tumor cell escape from the innate immune response.
KW - NK cell-activating receptors
KW - NKG2DL
KW - NSCLC
KW - Tumor-infiltrating NK cells
UR - http://www.scopus.com/inward/record.url?scp=45749134656&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxn038
DO - 10.1093/intimm/dxn038
M3 - Article
C2 - 18441340
AN - SCOPUS:45749134656
SN - 0953-8178
VL - 20
SP - 801
EP - 810
JO - International Immunology
JF - International Immunology
IS - 7
ER -