Dpj. Barton et al., EXPRESSION OF INTERLEUKIN-2 RECEPTOR-ALPHA (IL-2R-ALPHA) MESSENGER-RNA AND PROTEIN IN ADVANCED EPITHELIAL OVARIAN-CANCER, Anticancer research, 14(3A), 1994, pp. 761-772
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.