Spontaneous human lymphocyte‐mediated cytotoxicity againts tumour target cells. I. The effect of malignant disease

Abstract

Spontaneous human lymphocyte-mediated cytotoxicity (SLMC) against tumour-cell targets was examined in a series of patients with localized or malignant disease, both treated and untreated, and patients with untreated chronic lymphocytic leukemia (CLL). The level of SLMC was assessed by means of two previously established assay systems; the xenogeneic assay involving the mouse mastocytoma line P815, and the allogeneic assay in which the human chronic myelogenous leukemia-derived line, K562, was used. The assay systems involve the use of Ficoll-Isopaque-separated, iron-plus-magnetism-purified lymphocytes in an overnight 51chromium release assay, and reflect the cytotoxic ability of human non-T, complement receptor-, Fc receptor-positive lymphocytes. In the present paper, lymphocytes from all normal donors tested showed significant activity in the SLMC assay, with some variation from day to day. This variation was markedly reduced when different normal donors were tested on the same day and under identical experimental conditions. In contrast, lymphocytes from many patients with malignant disease had decreased SLM activity, and this decrease was highly significant in patients with treated or untreated metastatic disease, or untreated CLL. This was also the case when the data were expressed relative to the number of cytotoxic cells in the normal control population, or in comparison to the relative SLMC activity of lymphocytes from patients with other conditions. Markedly decreased SLMC was observed in some patients in spite of normal T and B lymphocyte proportions, or the presence of the ability to mount a vigorous delayed hypersensitivity reaction to PPD. A comparison of the xenogeneic and allogeneic assays showed that the same information with respect to whether SLMC was normal or abnormal was obtained with both assays in the majority of cases. The significance of the data is discussed with respect to the possible role of SLMC in vivo and the relevance of SLMC to the assessment of specific cell-mediated cytotoxicity in malignant disease.

Relationship of natural killer-cell activity to rhesus antigens in man

“…Analysis of the clinical data, however, revealed no such bias in patient management. It is also known that NKcell activity is decreased in patients with disseminated tumours Pross & Baines, 1976) but again, analysis of our data revealed no significant difference between the proportion of patients with disseminated melanoma in the Rh-and Rh+ groups. These considerations of course do not apply to the studies on normal subjects.…”

Natural killer (NK) activity in peripheral blood lymphocytes of patients with benign and malignant breast disease

“…Indeed, in animal models the genetically determined level of NK activity influences both the growth rate of tumour implants (Kiessling & Wigzell, 1979) and outgrowth of experimental metastases (Hanna, 1980). Studies of NK activity of patients with neoplastic diseases have shown a reduction in comparison with control populations and reduced activity is most clearly displayed in individuals with advanced neoplasia (Pross & Baines, 1976;Menon & Stefani, 1978;Takasugi et al, 1977).…”

A humoral cytotoxic substance produced by a human killer cell line

“…Subsequently it was shown that the cells which are involved in SLMC have both Fe and C3 receptors (Pross and Baines, 1976) and that they develop in vitro into SmIg-positive lymphocytes (Chess, Levine and MacDermott, 1975). Pross an(d Baines (1976) also demonstrated that lymphocytes from normal donors showed significant activity in SLMC assay, while lymphocytes from many patients with malignant disease had markedly decreased SLMC.…”