Lymphokine-activated killer cell suppressor factor in malignant effusions

J. J. Pelton, D. D. Taylor, W. C. Fowler, C. G. Taylor, N. Z. Carp and J. L. Weese
Department of Surgical Oncology, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, Pa 19111.

We examined the possibility that tumor-released products inhibit lymphokine-activated killer cell activation. Lymphokine-activated killer cells from human peripheral blood lymphocytes were activated with recombinant interleukin 2 for 4 days in the presence of malignant effusions or conditioned media from cultured cell lines (10% vol/vol). Eight of 10 malignant effusions/media suppressed the induction of lymphokine-activated killer cell cytotoxicity, as measured in a 4-hour sodium chromate release assay. Seven of 10 effusions/media inhibited lymphokine-activated killer cell proliferation. Suppression was both dose and time dependent. A representative suppressive effusion was fractionated by agarose gel chromatography, treated with detergents disruptive of ionic bonds and lipids, and refractionated using polyacrylamide gel chromatography. Seven suppressive fractions ranging in molecular weight from 1 x 10(5) to 3 x 10(5) d were isolated. It is speculated that this suppressor factor may represent a large multimeric structure with ionic-bonded individual suppressive components.