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

Suppression of various functions of T cells derived from cancer patients has been linked previously to changes in the T-cell receptor (TCR)-associated signal transduction molecules, in particular the zeta chain of the TCR complex. In this study, we have examined the TCR zeta chain expression and cytokine production lit vivo and in vitro in T cells of patients with metastatic adenocarcinomas of the pancreas that participated in a Phase I clinical trial of the MUC1 peptide plus bacillus Calmette-Guerin cancer vaccine. A majority of the patients had reduced TCR zeta chain expression and interleukin 4 production by T cells, and all of the patients showed decreased production of IFN-gamma of their peripheral T cells when compared with healthy individuals. Peripheral blood T cells were activated with the phorbol ester phorbol myrisate acetate and ionomycin to show that although aberrant TCR zeta chain expression and decreased cytokine production were often correlated, the reduced cytokine production was not simply a consequence of an impaired TCR zeta chain expression. Rather, these are two separate but parallel defects in signal transduction in T cells, which are potentially modulated by the same mechanisms, Half of the patients showed an improvement for TCR zeta chain or IFN-gamma expression after vaccination.