Expression of interleukin-2 receptor alpha (IL-2R alpha) mRNA 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 cellular source of sIL-2R alpha, the expression of IL-2R alpha was assessed at the mRNA and protein level in peripheral blood mononuclear cells (PBMC), in ovarian cancer ascitic cell infiltrates and in primary and metastatic epithelial ovarian cancer lesions by immunochemistry, by flow cytometric analysis and by in situ hybridization (ISH). Normal PBMC and the PBMC from ovarian cancer patients had a low or undetectable level of IL-2R alpha mRNA and of IL-2R alpha cell-surface protein expression. 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 were IL-2R alpha+. Cytologically these IL-2R alpha+ cells were lymphocytes. Frozen sections of primary and metastatic ovarian cancer lesions showed sparse lymphocytic infiltration and very small numbers of these 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 IL-2R alpha mRNA, there was a wide range in the level of mRNA expression in these positive cells. The cells expressing IL-2R alpha mRNA had the cytologic characteristics of lymphocytes. Similarly, in the frozen sections of the solid tumours, there was a range in the level of IL-2R alpha mRNA expression in the few TIL that expressed IL-2R alpha. Importantly, ovarian cancer cells and mesothelial cells did not express IL-2R alpha mRNA or IL-2R alpha protein. Our observations lead us to conclude that lymphocytes are the main, if not the only, source of sIL-2R alpha in ovarian cancer patients. Although cells expressing IL-2R alpha were relatively few in number, as the source of the high levels of sIL-2R alpha, they may contribute to the immunosuppression of ascitic lymphocytes in advanced epithelial ovarian cancer.