Studies on the mechanisms of decreased Lymphokine Activated Killer cell activity (LAK activity) in patients with hepatocellular carcinoma (HCC)

肝細胞癌患者(HCC)のlymphokine activated killer細胞活性(LAK活性)正常群, LAK活性低値群,および健常者を対象に末梢血単核球から誘導されるLAK活性の発現に関与する因子を検討し, HCCにおけるLAK活性低下の機序を検討した. 1)健常者およびHCCのLAK活性の誘導は抗gamma interferon (γ-IFN)抗体添加により抑制された. HCCのLAK活性誘導時のγ-IFN産生能は低下しており, γ-IFN添加によりLAK活性の増強を認めた.したがって, LAK活性誘導にγ-IFNの関与が示唆された. 2)HCC末梢血単核球亜分画は健常者と比べ有意の変動を示さなかった.健常者,およびLAK活性正常HCC群において, Leu 7あるいはLeu 11b分画除去によりLAK活性および培養上清中γ-IFN濃度は低下するが, LAK活性低値HCC群に比しLAK活性は依然高い活性を示した.また,その分画除去により低下したLAK活性はγ-IFN添加により有意の増強が認められなかった.以上の成績より, HCCのLAK活性低下はγ-IFN産生障害のみでなく, LAK前駆細胞としての広範な単核球系の異常の関与が推察された.

[1]  利治 西原,et al.  肝細胞癌患者におけるLymphokine activated killer細胞活性と臨床的及び免疫学的成績との比較検討 , 1988 .

[2]  G. Marshall,et al.  Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. , 1987, The New England journal of medicine.

[3]  N. Damle,et al.  Interleukin 2-activated human killer cells are derived from phenotypically heterogeneous precursors. , 1986, Journal of immunology.

[4]  A. Chang,et al.  Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. , 1985, The New England journal of medicine.

[5]  S. Hinuma,et al.  Comparison of the biological properties of purified natural and recombinant human interleukin-2. , 1985, Biochemical and biophysical research communications.

[6]  L. Lanier,et al.  Recombinant interleukin 2 enhanced natural killer cell-mediated cytotoxicity in human lymphocyte subpopulations expressing the Leu 7 and Leu 11 antigens. , 1985, Journal of immunology.

[7]  C. Balch,et al.  Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells. , 1985, Journal of immunology.

[8]  J. Werkmeister,et al.  In vitro generation of human activated lymphocyte killer cells: separate precursors and modes of generation of NK-like cells and "anomalous" killer cells. , 1984, Journal of immunology.

[9]  J. Roth,et al.  Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells , 1983, The Journal of experimental medicine.

[10]  D. Weigent,et al.  Potentiation of lymphocyte natural killing by mixtures of alpha or beta interferon with recombinant gamma interferon , 1983, Infection and immunity.

[11]  M. Kew,et al.  Depressed natural killer cell activity in patients with hepatocellular carcinoma in vitro effects of interferon and levamisole , 1982 .

[12]  T. Waldmann,et al.  A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor , 1982, Nature.

[13]  S. Rosenberg,et al.  Lymphokine-activated killer cell phenomenon. Lysis of natural killer- resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes , 1982, The Journal of experimental medicine.

[14]  T. Waldmann,et al.  A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. , 1981, Journal of immunology.

[15]  W. Farrar,et al.  Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2. , 1981, Journal of immunology.