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Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocyte/tumor culture activated by interleukin-12 plus interleukin-2, and the phenotypic characterization of the cells in patients with advanced carcinoma

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Abstract

In this study, we evaluated the ability of combination regimens of interleukin-12 (IL-12) and interleukin-2 (IL-2) to induce effective killer cells against human tumors in vitro, in peripheral blood lymphocytes (PBL) from 15 cancer patients and mixed lymphocyte/tumor culture (MLTC) cells from 16 cancer patients, and carried out a phenotypic analysis of the cells responsible for the lysis of the human tumors. The freshly prepared PBL were cultivated with IL-2 alone or IL-12/IL-2 for 10 days [lymphokine-activated killer (LAK) cell generation system]. The MLTC cells (PBL cultured with mitomycin-C-treated allogeneic G-415 tumor cells for 3 days) were further cultivated with IL-2 or IL-12/IL-2 for 7 days [cytotoxic T lymphocytes (CTL) generation system]. The cytolytic activities of the lymphoid cells cultivated with IL-12/IL-2 were significantly augmented in both the LAK and CTL generation systems, as compared with those of cells treated with IL-2 alone. In the LAK generation system, the cytolytic activities of the cells cultivated with IL-12/IL-2 were significantly decreased by the method of negative selection of CD11b+ or CD56+ cells using immunomagnetic beads. The CD8+-depleted cells showed a slight decrease of activity. The killer cell activities of the CD4+-depleted cells remained unchanged. In the CTL generation system, the activity was markedly reduced by the elimination of the CD8+ or CD11b+ or CD56+ cells. The combined data suggested that IL-12/IL-2-induced killer effector cells in the LAK generation system were mainly of the natural killer (NK) type, comprising CD8−CD11b+, CD8− CD16b−, CD3−CD56+, and partly possible CD8+ CD11b−T cells. CD8+ CD11b−T cells mixed with cells of the NK type, comprising CD8−CD11b+, CD8− CD16b− and CD3−CD56+ cells, were the population of killer effector cells induced by IL-12/IL-2 in the CTL generation system.

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Abbreviations

IL :

interleukin

LAK :

lymphokine-activated killer

CTL :

cytotoxic T lymphocytes

PBL :

peripheral blood lymphocytes

NK :

natural killer

MLTC :

mixed lymphocyte/tumor cell culture

TIL :

tumor-infiltrating lymphocytes

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  1. Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki 305, Japan

    Shohei Koyama

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  1. Shohei Koyama
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Koyama, S. Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocyte/tumor culture activated by interleukin-12 plus interleukin-2, and the phenotypic characterization of the cells in patients with advanced carcinoma. J Cancer Res Clin Oncol 123, 478–484 (1997). https://doi.org/10.1007/BF01192201

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  • DOI: https://doi.org/10.1007/BF01192201

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