Variable expression of CD3‐ζ chain in tumor‐infiltrating lymphocytes (TIL) derived from renal‐cell carcinoma: Relationship with til phenotype and function

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Abstract
It has been reported that in mice and in humans, tumor‐infiltrating lymphocytes (TIL) may exhibit a defect in CD3‐ζ‐chain expression. Therefore, the level of CD3‐ζ was analyzed in TIL derived from patients with renal‐cell carcinoma, and its correlation with TIL phenotype and function was assessed. We identified 4 out of 13 tumor‐infiltrating lymphocytes derived from renal‐cell carcinoma, with a significant decrease in CD3‐ζ‐chain expression as compared with control peripheral‐blood lymphocytes. This defect was never found after culturing TIL with IL2. In one case, the low expression of ζ chain observed in TIL on day 0 was reversed when TIL were cultured with IL2. The ζ‐chain level did not seem to predict the growth of TIL in response to IL2. All the TIL, irrespective of the level of ζ‐chain expression, exhibited lower proliferative response when stimulated with PHA or anti‐CD3 MAb in comparison with normal peripheral‐blood mononuclear cells. Nevertheless, in this limited series of patients, a correlation was observed between the level of ζ‐chain expression and T‐cell infiltration (p = 0.02). After TIL stimulation with PHA or anti‐CD3, in contrast to IL2 or IFNγ production, a trend towards a relationship between TNF α induction and the level of ζ‐chain expression was observed.