title: Variable expression of CD3-zeta chain in tumor-infiltrating lymphocytes (TIL) derived from renal-cell carcinoma: relationship with TIL phenotype and function.
abstract: It has been reported that in mice and in humans, tumor-infiltrating lymphocytes (TIL) may exhibit a defect in CD3-zeta-chain expression. Therefore, the level of CD3-zeta 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-zeta-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 zeta chain observed in TIL on day 0 was reversed when TIL were cultured with IL2. The zeta-chain level did not seem to predict the growth of TIL in response to IL2. All the TIL, irrespective of the level of zeta-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 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 TNF alpha induction and the level of zeta-chain expression was observed.
authors.affiliation: Département de Biologie Clinique, Institut Curie, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Tartour
authors.forename: S
authors.initials: S
authors.lastname: Latour
authors.forename: C
authors.initials: C
authors.lastname: Mathiot
authors.forename: N
authors.initials: N
authors.lastname: Thiounn
authors.forename: V
authors.initials: V
authors.lastname: Mosseri
authors.forename: I
authors.initials: I
authors.lastname: Joyeux
authors.forename: C D
authors.initials: CD
authors.lastname: D'Enghien
authors.forename: R
authors.initials: R
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Debre
authors.forename: W H
authors.initials: WH
authors.lastname: Fridman
mesh_terms: D017252:CD3 Complex / Q000737:chemistry / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma