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T Cells from Renal Cell Carcinoma Patients Exhibit an Abnormal Pattern of B-specific DNA-binding Activity: A Preliminary Report¹

Departments of Immunology [X. L., J. L., J-K. P., T. A. H., P. R., J. F.], Urology [E. K.], Anatomic Pathology [M. E., R. T.], and Hematology-Oncology [R. B.], The Cleveland Clinic Foundation, Cleveland, Ohio 44195

Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to B/Rel family proteins, the B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-B1 (p50) subunit. The second abnormality in B-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-B complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli.

¹ This work was supported in part by USPHS Grant CA 56937.

² To whom requests for reprints should be addressed, at The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.

Received 5/11/94. Accepted 8/17/94.

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