EXPRESSION OF INTERLEUKIN-2 RECEPTOR-ALPHA (IL-2R-ALPHA) MESSENGER-RNA AND PROTEIN IN ADVANCED EPITHELIAL OVARIAN-CANCER

Advanced epithelial ovarian cancer has recently been identified by us to be associated with elevated serum and ascitic levels of the soluble Interleukin-2 receptor alpha (sIL-2R alpha). To determine the cellula r source of sIL-2R alpha, the expression of IL-2R alpha was assessed a t the mRNA and protein level in peripheral blood mononuclear cells (PB MC), in ovarian cancer ascitic cell infiltrates and in primary and met astatic epithelial ovarian cancer lesions by immunochemistry, by flow cytometric analysis and by in situ hybridization (ISH). Normal PBMC an d the PBMC from ovarian cancer patients had a low or undetectable leve l of IL-2R alpha mRNA and of IL-2R alpha cell-surface protein expressi on. Flow cytometric analysis of the heterogeneous ascitic infiltrates revealed few cells positively expressing cell-surface IL-2R alpha. By immunocytochemistry, 1-2% of leukocytes in the ascitic infiltrates wer e IL-2R alpha(+). Cytologically these IL-2R alpha(+) cells were lympho cytes. Frozen sections of primary and metastatic ovarian cancer lesion s showed sparse lymphocytic infiltration and very small numbers of the se tumour infiltrating lymphocytes (TIL) were IL-2R alpha(+). In situ hybridization demonstrated that although less than 2% of leukocytes in the ascitic infiltrate had detectable levels of lL-2R alpha mRNA, the re was a wide range in the level of mRNA expression in these positive cells. The cells expressing IL-2R alpha mRNA had the cytologic charact eristics of lymphocytes. Similarly, in the frozen sections of the soli d tumours, there was a range in the level of IL-2R alpha mRNA expressi on in the few TIL that expressed IL-2R alpha. Importantly, ovarian can cer cells and mesothelial cells did not express IL-2R alpha mRNA or IL -2R alpha protein. Our observations lead us to conclude that lymphocyt es are the main, if not the only, source of slL-2R alpha in ovarian ca ncer patients. Although cells expressing IL-2R alpha were relatively f ew in number, as the source of the high levels of sIL-2R alpha, they m ay contribute to the immunosuppression of ascitic lymphocytes in advan ced epithelial ovarian cancer.