ALTERED CD3 CHAIN AND CYTOKINE GENE-EXPRESSION IN TUMOR-INFILTRATING T-LYMPHOCYTES DURING THE DEVELOPMENT OF MESOTHELIOMA

The mechanisms whereby tumors escape immunosurveillance remain poorly understood. De-activation or deviation of T lymphocyte responses may o ccur following exposure to tumor-associated or -derived signals. In th e present study it is demonstrated that during development of syngenei c malignant mesothelioma in mice, the relative CD3 delta, CD3 gamma an d CD3 zeta/eta mRNA levels expressed by tumor infiltrating lymphocytes (TIL) decrease, while CD3 epsilon mRNA levels remain relatively const ant. Expression of IFN gamma mRNA by TIL decreased during tumor develo pment, while IL-2 mRNA levels showed slight increases. IL-3 mRNA was n ot detected at any time during tumor development and IL-4 transcripts were only detected in the later stages of tumor development, In the sp leens of tumor-bearing mice, IL-2 transcripts were detected throughout the time course from days 1 to 22(24), while IFN gamma mRNA was only detected at early times from days 0-13. Previous work demonstrated a r ole for tumor cell-derived TGF beta in the immunobiology of mesothelio ma. Here it is shown that the suppression of CD3-subunit expression by TIL was ameliorated in tumors where TGF beta-expression was reduced b y inducible TGF beta-specific antisense-RNA, thus, suggesting that lym phocytes may become de-activated upon infiltration of the tumor microe nvironment.