Abstract
Tumour-infiltrating lymphocytes (TILS) are often difficult to expand in vitro. In some cases this has been attributable to immunosuppression mediated by the elaboration of prostaglandins by either tumor cells or tumor-infiltrating monocytes. In this laboratory, freshly prepared TILs containing single-cell suspensions of head and neck tumors displayed both poor proliferation as well as minimal responsiveness to indomethacin-mediated reversal of immunosuppression. In order to investigate tumor-mediated immunosuppression further, a system was developed whereby a new cell line of head and neck squamous cell carcinoma was used to suppress allogeneic peripheral blood mononuclear cell proliferation in response to phytohemagglutinin (PHA) and interieukin-2 (IL-2). Tumor cells were able to suppress peripheral blood mononuclear cell (PBMNC) proliferation up to 95%. This suppressive effect was dependent on tumor cell number and was reversible by the use of higher concentrations of PHA, but not by increased concentrations of IL-2. Suppression was immediate when IL-2 was used as the stimulus for proliferation, but required extended lymphocyte/tumor cell contact when PHA was used. Flow cytometric analysis of tumor-exposed and PHA-stimulated PBMNCs revealed a decrease in both the number of cells expressing IL-2 receptors as well as the density of IL-2 receptors per cell. This pattern of suppression, as well as the reversibility of suppression by indomethacin, implicates prostaglandins in the mechanisms by which these tumor cells mediate immunosuppression.
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