Role of alloantigens in natural killing. Allogeneic but not autologous tumor biopsy cells are sensitive for interferon-induced cytotoxicity of human blood lymphcoytes.

Abstract

Blood lymphocytes of patients with solid tumors were assayed for cytotoxicity against autologous and allogeneic primary tumor cells. The lymphocytes killed autologous tumor cells in 7 of 25 cases (28%) and allogeneic tumor cells in 2 of 37 tests (5%). Lymphocytes from healthy donors were rarely cytotoxic for the biopsy cells, which indicates that these cells have low natural kill sensitivity. The autoreactivity that may reflect the immunological recognition of tumor cells was not altered by pretreatment of the effectors with interferon (IF). In contrast, killing of allogeneic tumor biopsy cells was induced by IF in approximately 50% of tests, with the lymphocytes of both the tumor patients and the healthy donors. The mechanism of the alloreactivity is most likely a consequence of IF-induced polyclonal activation of cytotoxic potential and the lymphocytes that are committed to recognize the alloantigens expressed on the particular target manifest the killing function. When the biopsy cells were explanted and kept in culture for 5-6 d, their susceptibility for the lymphocyte damage increased, and they were killed by the IF-treated cells also in autologous combinations. Whether this change in sensitivity is a result of qualitative or quantitative changes in antigen expression or of other changes in the properties of the cell membrane is unknown.

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

“…shown to augment NK activity and to stimulate lysis of allogeneic but not of autologous fresh tumors (33,34). Because IF is known to be present in PP-TCGF, we tested whether IF and not IL-2, as presumed, was the primary stimulus for LAK.…”

Effect of a streptococcal preparation (OK432) on natural killer activity of tumour-associated lymphoid cells in human ovarian carcinoma and on lysis of fresh ovarian tumour cells

“…Fresh tumour cells from human neoplastic tissues are generally resistant to natural cytotoxicity as measured by conventional cytolysis assays (Pattengale et al, 1982;Serrate et al, 1982;Vanky et al, 1980;Verkmeister et al, 1979;Vose et al, 1977aVose et al, , 1977bVose et al, , 1978Vose & Moore, 1980;Zarling et al, 1979). In a study with various human tumours, mainly of mesenchymal origin, Vanky et al reported that IFN-induced killing of fresh biopsy cells only if allogeneic combinations of PBL and target cells were used (Vanky et al, 1980).…”

“…In a study with various human tumours, mainly of mesenchymal origin, Vanky et al reported that IFN-induced killing of fresh biopsy cells only if allogeneic combinations of PBL and target cells were used (Vanky et al, 1980). Killing of fresh leukaemic targets by normal allogeneic effectors was reported by Moore et al (1982).…”

“…Unlike cell lines, fresh tumour cells are usually relatively resistant to natural cytotoxicity by unstimulated effector cells (Moore et al, 1982;Pattengale et al, 1982;Serrate et al, 1982;Vanky et al, 1980;Verkmeister et al, 1979;Vose et al, 1977a, b;Vose & Moore, 1980;Zarling et al, 1979). Vanky et al, (1980) showed that in various Correspondence: F. Colotta. Received 21 April 1983; accepted 8 July 1983. human tumours IFN could induce or augment cytotoxicity against fresh neoplastic cells provided allogeneic combinations of effectors and targets were studied.…”

Human natural killing against ovarian carcinoma

“…A concentration of 30-120 units/well was used in NK assays. In vitro culturing of some tumour cells has been known to alter their susceptibility to NK (Vanky et al, 1980;de Vries et al, 1975 (Table I). However, IFN failed to induce any activity against the resistant Cx680.…”