Suppressed T-cell receptor zeta chain expression and cytokine production in pancreatic cancer patients

Suppression of various functions of T cells derived from cancer patients ha s been linked previously to changes in the T-cell receptor (TCR)-associated signal transduction molecules, in particular the zeta chain of the TCR com plex. In this study, we have examined the TCR zeta chain expression and cyt okine production lit vivo and in vitro in T cells of patients with metastat ic adenocarcinomas of the pancreas that participated in a Phase I clinical trial of the MUC1 peptide plus bacillus Calmette-Guerin cancer vaccine. A m ajority of the patients had reduced TCR zeta chain expression and interleuk in 4 production by T cells, and all of the patients showed decreased produc tion of IFN-gamma of their peripheral T cells when compared with healthy in dividuals. Peripheral blood T cells were activated with the phorbol ester p horbol myrisate acetate and ionomycin to show that although aberrant TCR ze ta chain expression and decreased cytokine production were often correlated , the reduced cytokine production was not simply a consequence of an impair ed TCR zeta chain expression. Rather, these are two separate but parallel d efects in signal transduction in T cells, which are potentially modulated b y the same mechanisms, Half of the patients showed an improvement for TCR z eta chain or IFN-gamma expression after vaccination.