Specificity of cell‐mediated cytotoxicity against human melanoma lines: Evidence for “non‐specific” killing by activated T‐cells

Abstract

The specificity of cell-mediated cytotoxicity against melanoma cells in vitro has been analyzed in a large number of studies with cells both from normal and melanoma subjects. As in a number of other, recent, similar human studies, no evidence for tumour specificity was found. Effector cells in peripheral blood responsible for the cytotoxic raction were examined by cell separation methods based on red cell rosette formation and separation through Hypaque-Ficoll mixtures. The evidence suggests that non-specificity results from killing by cells separating largely in the non-sheep red blood cell rosetting fraction and which have cytotoxic specificity directed broadly to cells with abnormal membranes. Further analysis revealed that the cells were non-phagocytic and did not bear receptors for complement. They appear to be activated into cell division and to bear surface receptors for the Fc portion of IgG. Additional evidence is presented suggesting that the cells mainly responsible are activated thymus-dependent cells present in the circulation of both tumour-bearing and normal subjects.

Relationship of cell-mediated cytotoxicity against melanoma cells to prognosis in melanoma patients

“…Both "melanoma-specific" and "foetal-like" antigens have been defined on its surface. The control Chaing liver-cell line (Commonwealth Serum Laboratories, Melbourne, Victoria) was previously shown not to have, either melanoma or "foetal-like" antigens on its surface (Hersey et al, 1975b results suggest an association between low CMC values against cultured melanoma cells in patients after surgical removal of their melanoma and the subsequent recurrence of melanoma. One of the main problems in interpreting these results was to know the extent to which the patients were free of tumour after apparent complete surgical removal.…”

“…Hellstrom et al, 1971), there has been considerable controversy regarding the specificity and nature of the effector cells mediating the cytotoxicity (Baldwin, 1975;Herberman and Oldham, 1975;Takasugi et al, 1974). There now appears to be a consensus of opinion that much of the cytotoxicity of mononuclear cells from blood of tumourbearing subjects is mediated by cells which are also found in non-tumourbearing subjects, and which have natural cytotoxic specificities for a wide range of tumour cells (Takasugi et al, 1974(Takasugi et al, , 1977aKiuchi and Takasugi, 1976;De Vries et al, 1975;Hersey et al, 1975b;West et al, 1977).…”

Target selectivity of interferon-induced human killer lymphocytes related to their Fc receptor expression.

“…The active population is heterogeneous with regard to its cell surface characteristics (2-7). The "null" subset, obtained after removal of surface immunoglobulin-positive cells and readily resetting T lymphocytes, is highly enriched in activity (2)(3)(4). This subset contains a high proportion of Fc receptor (FcR)-positive cells.…”

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

“…The nature of NK cells is still controversial, although many workers agree they are neither B lymphocytes nor macrophages. Recent studies by West et al (1977) have supported the notion that they may be a sub-class of T lymphocytes (Hersey et al, 1975) but the question is far from settled.…”