Inhibition of lymphokine-activated killer cell generation by cultured tumor cell lines in vitro

• Published in: Cancer Immunology Immunotherapy Vol. 28; no. 1; pp. 43 - 53
• Main Authors: GUILLOU, P. J, SEDMAN, P. C, RAMSDEN, C. W
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1989; Springer-Verlag
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cell Adhesion; Cell Line; Cell Separation; Cell-Free System; Culture Media; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic - radiation effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunosuppression Therapy; Interferons; Interleukin-2 - biosynthesis; Killer Cells, Natural - immunology; Killer Cells, Natural - radiation effects; Kinetics; Lymphocyte Activation - radiation effects; Organs and cells involved in the immune response; Original; Tumor Cells, Cultured - immunology; Tumor Cells, Cultured - radiation effects; Cell culture; Mixed cell culture; Interleukin 2; Immunotherapy; Production; Cellular immunity; Inhibition; Lymphocyte; Tumor cell
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/BF00205800

The co-culture of human peripheral blood mononuclear cells (PBMC) with high concentrations of interleukin 2 normally generates lymphokine-activated killer (LAK) cells capable of indiscriminate lysis of tumor targets. However, the addition of certain cell-line-derived tumor cells to the LAK generation cultures within the first 48 h of culture initiation resulted in the suppression of the LAK cytotoxicity measured after 3-4 days of culture. Suppression could be achieved with tumor cell:PBMC ratios as low as 1:50 when tumor cells were derived from melanoma and colorectal cancer (G361, COLO320, HT-29), but suppression was not observed with cells from the breast cancer cell line SKBr3. No suppression of LAK generation was observed with normal epithelial cells from colon or breast, with autologous or allogeneic lymphoblasts, or with allogeneic vascular endothelial cells. Suppression was independent of the removal of adherent cells from PBMC, could not be prevented by indomethacin and was not attributable to interleukin 2 absorption/adsorption by tumor cells. The suppressive activity of some tumor cells could be augmented by preculture in recombinant gamma interferon. Serum-free supernatants from G361, COLO320 and HT-29 (but not SKBr3 or endothelial cells) were also highly suppressive towards the generation of LAK cells. The elaboration by tumor cells of factors capable of inhibiting LAK generation may partially explain the failure of LAK/interleukin 2 therapy in some experimental and clinical protocols.