IMPAIRED EXPRESSION AND FUNCTION OF SIGNAL-TRANSDUCING ZETA-CHAINS INPERIPHERAL T-CELLS AND NATURAL-KILLER-CELLS IN PATIENTS WITH PROSTATE-CANCER

Detection of functional circulating T cells and NK cells may serve as a clinical test for the selection of individuals who can benefit from immunotherapy. Incidence of the T-cell receptor zeta (TCR zeta) chain within these populations appears to correlate with adequate effector c ell function. In patients with advanced malignancy, the absence or red uced expression of zeta chain has been documented. Flow cytometric ana lysis in the present study revealed a significant reduction in zeta ch ain expression in peripheral blood lymphocytes (PBL) of 14 of 22 prost ate cancer patients (P < 0.000001) as compared to normal donors, appar ent in both T cells (CD3+, CD4+, CD8+), and NK (CD16+) cells. Compared to normal donor PBL, patient PBL cultured in the presence of CD3 and CD28, also demonstrated reduced expression of CD69 and/or CD25, and in some cases, failed to activate at all. Furthermore, evidence of cell proliferation in activation-stimulated patient PBL was muted: average PCNA positivity equaled 14%, a marked difference from what was observe d in normal donors (P < 0.0002), In 8 of 16 samples of PBL, where zeta expression was originally low, zeta levels returned to the normal ran ge after 48 hour culture in serum-free medium, suggesting that the los s of zeta is reversible and may be caused by a tumor-derived substance . These data support the premise that monitoring the expression of zet a in a cancer patient may provide a unique insight into the immune sta tus and functionality of the individual, with the potential to redirec t or augment therapies and ultimately alter prognosis. (C) 1998 Wiley- Liss, Inc.