Barton D P, Blanchard D K, Wells A F, Nicosia S V, Roberts W S, Cavanagh D, Djeu J Y
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, University of S. Florida College of Medicine, Tampa.
Anticancer Res. 1994 May-Jun;14(3A):761-72.
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.
我们最近发现，晚期上皮性卵巢癌与血清及腹水中可溶性白细胞介素-2受体α（sIL-2Rα）水平升高有关。为确定sIL-2Rα的细胞来源，我们通过免疫化学、流式细胞术分析及原位杂交（ISH），对外周血单个核细胞（PBMC）、卵巢癌腹水细胞浸润物以及原发性和转移性上皮性卵巢癌病灶中的IL-2Rα在mRNA和蛋白质水平的表达进行了评估。正常PBMC以及卵巢癌患者的PBMC中，IL-2Rα mRNA和IL-2Rα细胞表面蛋白表达水平较低或无法检测到。对异质性腹水浸润物进行流式细胞术分析显示，阳性表达细胞表面IL-2Rα的细胞很少。通过免疫细胞化学检测，腹水浸润物中1%-2%的白细胞为IL-2Rα阳性。从细胞学角度来看，这些IL-2Rα阳性细胞为淋巴细胞。原发性和转移性卵巢癌病灶的冰冻切片显示淋巴细胞浸润稀疏，这些肿瘤浸润淋巴细胞（TIL）中只有极少数为IL-2Rα阳性。原位杂交表明，尽管腹水浸润物中不到2%的白细胞可检测到IL-2Rα mRNA水平，但这些阳性细胞的mRNA表达水平差异很大。表达IL-2Rα mRNA的细胞具有淋巴细胞的细胞学特征。同样，在实体瘤的冰冻切片中，少数表达IL-2Rα的TIL中，IL-2Rα mRNA表达水平也存在差异。重要的是，卵巢癌细胞和间皮细胞不表达IL-2Rα mRNA或IL-2Rα蛋白。我们的观察结果使我们得出结论，淋巴细胞是卵巢癌患者sIL-2Rα的主要（即便不是唯一）来源。尽管表达IL-2Rα的细胞数量相对较少，但作为高水平sIL-2Rα的来源，它们可能在晚期上皮性卵巢癌中导致腹水淋巴细胞的免疫抑制。
