Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice

Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8$^+$ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-α and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3γ and completely lacked CD3ζ, which was replaced by the Fc$_\epsilon$ γ-chain. Expression of the tyrosine kinases p56$^{lck}$ and p59$^{fyn}$ was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.