VARIABLE EXPRESSION OF CD3-ZETA CHAIN IN TUMOR-INFILTRATING LYMPHOCYTES (TIL) DERIVED FROM RENAL-CELL CARCINOMA - RELATIONSHIP WITH TIL PHENOTYPE AND FUNCTION

It has been reported that in mice and in humans, tumor-infiltrating ly mphocytes (TIL) may exhibit a defect in CD3-zeta-chain expression. The refore, the level of CD3-zeta was analyzed in TIL derived from patient s with renal-cell carcinoma, and its correlation with TIL phenotype an d function was assessed. We identified 4 out of 13 tumor-infiltrating lymphocytes derived from renal-cell carcinoma, with a significant decr ease in CD3-zeta-chain expression as compared with control peripheral- blood lymphocytes. This defect was never found after culturing TIL wit h IL2. In one case, the low expression of zeta chain observed in TIL o n day 0 was reversed when TIL were cultured with IL2. The zeta-chain l evel did not seem to predict the growth of TIL. in response to IL2. Al l the TIL, irrespective of the level of zeta-chain expression, exhibit ed lower proliferative response when stimulated with PHA or anti-CDS M Ab in comparison with normal peripheral-blood mononuclear cells. Never theless, in this limited series of patients, a correlation was observe d between the level of zeta-chain expression and T-cell infiltration ( p = 0.02). After TIL stimulation with PHA or anti-CD3, in contrast to IL2 or IFN gamma production, a trend towards a relationship between TN F alpha induction and the level of zeta-chain expression was observed. (C) 1995 Wiley-Liss, Inc.