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.
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.
Koyama
S
S
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
D000368:Aged; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007167:Immunotherapy; D018664:Interleukin-12 / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*
D007376:Interleukin-2; D018664:Interleukin-12