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 occur following exposure to tumor-associated or -derived signals. In the present study it is demonstrated that during development of syngeneic malignant mesothelioma in mice, the relative CD3δ, CD3γ and CD3ζη mRNA levels expressed by tumor infiltrating lymphocytes (TIL) decrease, while CD3ε mRNA levels remain relatively constant. Expression of IFNγ mRNA by TIL decreased during tumor development, while IL-2 mRNA levels showed slight increases. IL-3 mRNA was not detected at any time during tumor development and IL-4 transcripts were only detected in the later stages of tumor development. In the spleens of tumor-bearing mice, IL-2 transcripts were detected throughout the time course from days 1 to 22(24), while IFNγ mRNA was only detected at early times from days 0–13. Previous work demonstrated a role for tumor cell-derived TGFβ in the immunobiology of mesothelioma. Here it is shown that the suppression of CD3-subunit expression by TIL was ameliorated in tumors where TGFβ-expression was reduced by inducible TGFβ-specific antisense-RNA, thus, suggesting that lymphocytes may become de-activated upon infiltration of the tumor micro-environment.