Abstract
T lymphocytes from patients with renal cell carcinoma (RCC) show reduced immune
function and impaired activation of the transcription factor, NF-κB. We
determined the mechanism of NF-κB suppression in T cells of RCC patient and
determined whether supernatant fluid from RCC explants (RCC-S) induced the same
phenotype of NF-κB suppression in normal T cells that is observed in patient
T cells. The pattern of κB-binding activity in T cells of RCC patient was
altered as compared to that seen in T cells obtained from normal volunteers. In
some patients, no activation of RelA/NFkappaB1-binding activity was detectable,
while in others κB-binding activity was modestly induced but the duration
was reduced. IκBα was degraded normally following stimulation in both
normal controls and T cells from RCC patients. RCC-S did not alter the
cytoplasmic levels of RelA and NF-κB1 but did suppress their nuclear
localization and inhibited the activation of RelA/NF-κB1 binding complexes.
These results show that RCC-S can induce in normal T cells the same phenotype of
impaired NF-κB activation that is detected in T cells of RCC patient. It
also appears that NF-κB suppression by RCC-S may contribute to the
immunosuppression of host immunity.