EXPRESSION OF CYTOKINE GENES OR PROTEINS AND SIGNALING MOLECULES IN LYMPHOCYTES ASSOCIATED WITH HUMAN OVARIAN-CARCINOMA

We have reported that tumor-associated T or natural killer (NK) lympho cytes purified from ascites of women with ovarian carcinoma show defec tive expression and function of signaling proteins, including reduced expression of TcR-zeta chains and p56(lck). In this study, the cytokin e profiles of both tumor cells and tumor-associated lymphocytes (TAL) recovered from the tumor milieu were examined. Expression of cytokine genes was studied by semi-quantitative RT-PCR and Southern hybridizati on, and the presence of intracellular cytokine proteins was confirmed by immunostaining. Levels of mRNA encoding the cytokine genes typicall y transcribed in activated T lymphocytes, including IFN-gamma, IL-2 an d IL-4, were markedly reduced, as was expression of the corresponding proteins, in TAL-T or TAL-NK cells relative to normal PBL-T or PBL-NK cells, respectively. Levels of TGF-beta and IL-6 were unaltered, while those of IL-10 were up-regulated. Although both tumor cells and TALs contributed to the enhanced level of IL-10 expression, a higher propor tion of TAL-T lymphocytes than normal PBL-T cells expressed IL-10 prot ein. The altered profile of cytokine genes and proteins in TALs, TAL-T or TAL-NK cells was associated with impaired expression and/or functi on of signaling molecules, zeta chain and p56(lck). Our data suggest t hat abnormalities in signal transduction commonly seen in lymphocytes obtained from the tumor micro-environment are related to the concomita ntly observed altered patterns of expression of cytokine transcripts a nd proteins. (C) 1996 Wiley-Liss, Inc.