Enhancement of depressed lymphokine activated killer cell activity in patients with hepatocellular carcinoma
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Hepatocellular carcinoma (HCC) patients can be divided into two groups according to the degree of lymphokine activated killer (LAK) cell activity; a high LAK activity group (H-LAK-HCC) and a low LAK activity group (L-LAK-HCC). Interferon-gamma (IFN-gamma) production is severely defective in L-LAK-HCC but not defective in H-LAH-HCC. IFN-gamma production is suppressed with the addition of anti-Tac in dose dependent manner, though LAK activity is suppressed only in the presence of high concentration of anti-Tac. LAK activity is suppressed with the addition of anti-IFN-gamma, which is most prominent when the antibody is present during the first 12 hr of incubation. LAK generation is enhanced with the addition of recombinant IFN-gamma, which is most prominent when it is present during the first 12 hr of incubation. However, this enhancing effect is less prominent in L-LAK-HCC as compared to normals, liver cirrhosis, and H-LAK-HCC. This enhancement is regarded to depend on the presence of Leu7+ and Leu11+ subset, as this enhancement is abandoned and IFN-gamma production is inhibited when either of these subsets is deleted. These data suggest that IFN-gamma production and the participation of Leu7+ and Leu11+ subsets is important in sufficient LAK generation, and that poor IFN-gamma production and insufficient response to IFN-gamma may be the cause of severely defective LAK generation in L-LAK-HCC.
Key wordshepatocellular carcinoma gamma-interferon interleukin 2 lymphokine activated killer cell
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- 2.Grimm EA, Ramsey KM, Mazumder A, Wilson DJ, Djeu JYL, Rosenberg SA. Lymphokine activated killer cells phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med 1983; 157: 884.PubMedGoogle Scholar
- 3.Grimm EA, Robb RJ, Roth JA, Neckers LM, Lachman LB, Wilson DJ, Rosenberg SA. Lymphokine activated killer cells phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells. J Exp Med 1983; 158: 1356.PubMedGoogle Scholar
- 5.Hsieh KH, Shu S Lee CS, Chu CT, Yang CS, Chang KJ. Lysis of primary hepatic tumours by lymphokine activated killer cells. Gut 1987; 28: 117–24.Google Scholar
- 7.Pross HF, Baines MG. Spontaneous human lymphocyte mediated cytotoxicity against tumor target cells. IV. A brief review. Cancer Immunol Immunother 1977; 3: 75–85.Google Scholar
- 10.Holdstock G, Chastenay BF, Krawitt. Studies on lymphocyte hyporesponse in cirrhosis. Am. J. Gastroenterol 1982; 82: 206.Google Scholar
- 11.Dilman RO, Koziol JA, Zavanelli MI. Immunoincompetence in cancer patients. Cancer 1984; 53: 144.Google Scholar
- 14.Naruo K, Hinuma S, Kato K. Comparison of the biological properties of purified natural and recombinant human interleukin-2. Biol Biophys Res Commun 1985; 128: 257–64.Google Scholar
- 17.Gerson JM. Systemic and in situ natural killer activity in tumor-bearing mice and patients with cancer. In: Herberman RB, ed. Natural cell-mediated immunity against tumors. New York: Academic Press, 1980; 1047–62.Google Scholar
- 21.Lotze MT, Matory YL, Ettinghausen SE, Rayner AA, Sharrow SO, Seipp CAY, Custer MC, Rosenberg SA. In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol 1985; 135: 2865.PubMedGoogle Scholar