Summary
The generation of lymphokine activated killer (LAK) cells by recombinant IL2 (rIL2) in collaboration with interferonγ (IFNγ) was examined in peripheral blood mononuclear cells (PBMC) from patients with malignant tumors of the digestive organs and breast cancer. LAK cytotoxicity could be induced by rIL2 at 10 units/ml in 10 of 12 patients and 20 of 37 using fresh autologous tumor cells and PK-1, an established solid tumor cell line as a target, respectively. Among 34 patients, in which titers of IFNγ produced were assayed, 12 showed no IFNγ production. All of these 12 patients had no or extremely low LAK activity, suggesting the correlation of LAK generation with the production of IFNγ in response to rIL2. LAK induction by rIL2 in PBMC of cancer patients was almost completely inhibited by addition of anti-IFNγ serum. Depressed LAK generation, which was accompanied by no or low levels of IFNγ production, was partially restored by addition of exogenous recombinant IFNγ. These results indicate that LAK induction by rIL2 in cancer patients involves the production of IFNγ and its interaction with rIL2.
The results also suggested the presence of a factor(s) suppressing LAK induction by rIL2 in the serum of cancer patients. Based on these results, the cancer patients could be divided into the following three groups. Group 1, in which the serum suppressor activity was undetectable, had the same level of LAK cytotoxicity in PBMC as healthy controls. Group 2 showed the serum suppressor factor and had the lower level of cytotoxicity in PBMC when cultivated in autologous serum (AS) compared to healthy controls. The depressed LAK induction in AS medium was restored to a normal level in culture with fetal calf serum (FCS) plus rIL2, or by addition of rIFNγ, or high concentrations of rIL2 in AS medium. The last group (group 3), in which the serum suppressor factor was also found, had the lowest level of cytotoxicity compared to healthy controls. The LAK induction in these patients could not be restored to a normal level by culture in FCS medium, addition of exogenous rIFNγ or high concentrations of rIL2, suggesting the possibility that the deficit of LAK generation in this group might involve the dysfunction or the lack of IL2 responder cells, in addition to the presence of a serum suppressor factor(s).
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Shiiba, K., Suzuki, R., Kawakami, K. et al. Interleukin 2-activated killer cells: generation in collaboration with interferonγ and its suppression in cancer patients. Cancer Immunol Immunother 21, 119–128 (1986). https://doi.org/10.1007/BF00199859
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DOI: https://doi.org/10.1007/BF00199859