Mononuclear-cell infiltration in ovarian cancer. II. Immune function of tumour and ascites-derived inflammatory cells

Abstract

Summary.-Mononuclear cell fractions were isolated from blood, ascites and solid tumours of patients undergoing surgery for Stages III and IV PHA responses of patient blood and ascites fractions were about half that of normal blood. Tumour-infiltrating lymphocytes (TIL) were less than 10% as responsive as normal blood. The depressed PHA responses of the TIL were not due to the presence of a suppressor cell population. NK activity of patient blood was less than that of normal blood, but not as much as the ascites or TIL cells. The activity of the ascites-derived lymphocytes was enhanced by treatment with interferon. ADCC activity against both CRBC and SB cells was normal or higher than controls in patient blood, and depressed in the ascites-derived fractions. TIL responded to <10% of the patient blood values.The results indicate a lack of response by ascitic and TIL cells in assays dependent on FcR -bearing effector cells and a greater loss of PHA-reactive cells from the tumour than from blood and ascites. These data could result from intratumour inactivation, or a failure of the particular subset to localize either In the ascites or the tumour site.

Mononuclear-cell infiltration in ovarian cancer. III. Suppressor-cell and ADCC activity of macrophages from ascitic and solid ovarian tumours

“…In general, NK-cell function was markedly depressed in human tumours (Vose et al, 1977a;Totterman et al, 1980;Mantovani et al, 1980a;Haskill et al, 1982b). Specifically cytotoxic T cells have only been detected in a few instances (Vose et al, 1977b;Werkmeister et al, 1979) suggesting that effector-cell function may be difficult to maintain in situ.…”

“…ADCC Activity of AscM and TuM ADCC assays were carried out against either the K-cell sensitive tumour target SB, or the monocyte-sensitive erythroid CRBC target cell. Previously, we reported that the blood mononuclear-cell fraction of these patients is frequently as active as that of normal donors in both these assays (Haskill et al, 1982b). TuM had significant activity in 2/4 cases against the monocyte-sensitive CRBC target cell (Fig.…”

“…Graded doses of cells were added to 104 nonadherent patient blood lymphocytes. Tumour cells, TIL (which are routinely unresponsive to PHA; Haskill et al, 1982b) ascites-derived macrophages (AscM) and a population of TuM sedimenting as fast as the AscM, failed to suppress the response. However, the slower-sedimenting population of TuM was effective.…”

“…Two classes were characterized; 1 sedimented at < 6 mm/h and was similar in size to most blood mononuclear cells; the other was composed of larger, strongly adherent macrophages distinct from blood monocytes, which sedimented with the tumour cells. In the second communication (Haskill et al 1982b) we investigated effector-cell functions (PHA, ADCC and NK) associated with blood and bloodequivalent inflammatory cells present in both ascitic and solid tumours. The data indicated that all tumour-derived effector-cell tests were markedly depres-sed, whilst only the ascites effector cells marked by FcR were depressed relative to patient blood.…”

Expression of MHC products and leucocyte differentiation antigens in gynaecological neoplasms: An immunohistological analysis of the tumour cells and infiltrating leucocytes

“…Functional studies showing depressed proliferative activity in T cells recovered from ovarian cancers implicated tumour inactivation as the cause, or failure of a particular subset to localise at the tumour site (Haskill et al, 1982a). An alternative explanation might be that the predominant T8 + subset contains functionally active suppressor cells (Vose & Moore, 1979).…”