Science · 1992 · 639 citations · 34 references
Life SciencesImmunologyOncologyCancer ImmunologyCellular ImmunologyTumor ImmunologyAntitumor T Cell ResponsesCytotoxic T Lymphocyte ResponsesT Cell ActivationT Cell BiologyT Cell Responses To TumorsTumor AntigensAdaptive Immune DefectsCd8 Positive T Cell ResponsesCytotoxic Effector FunctionCytotoxic T Lymphocyte FunctionSignal Transduction AlterationT Cell CytotoxicityT Cell ReceptorsT-cell Responses To Tumor Antigens
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-alpha 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 CD3 gamma and completely lacked CD3 zeta, which was replaced by the Fc epsilon gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.
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