Deficient T cell immune function and intracellular signaling in
cancer patients may result from effects of
tumors or their products on lymphocytes. Recently, it was demonstrated that several ovarian
carcinoma cell lines could produce soluble factors that inhibited T cell proliferation. The aim of this study is to assess the effect of supernatants from 3 ovarian
carcinoma cell lines (OVCAR3, CAOV3, SKOV3) on signal transduction elements that are linked to the IL-2R and its JAK-STAT pathway. A profound inhibition of proliferation, lower level of IFN-gamma and higher level of
IL-10 gene expression were observed when CD8+ T cells were co-cultured with supernatants from 3 ovarian
carcinoma cell lines. Cell cycle studies on inhibited CD8+ T cells showed most of them were growth arrested in G0/G1 phase. Western blot analysis showed that
tumor supernatants suppressed expression of JAK3 and
tyrosine phosphorylation of STAT5. JAK1 was not altered and the inhibition of STAT3 only appeared in OVCAR3 cells.
Tumor supernatants also partially blocked induction of
IL-2R beta and gamma chains expression. These findings suggest that ovarian
carcinoma cells may suppress T cell proliferation through inhibition
IL-2 dependent signaling pathways, which may be a mechanism of ovarian
carcinoma induced immunosuppression.