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 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.
Tartour
E
E
Département de Biologie Clinique, Institut Curie, Paris, France.
Latour
S
S
Mathiot
C
C
Thiounn
N
N
Mosseri
V
V
Joyeux
I
I
D'Enghien
C D
CD
Lee
R
R
Debre
B
B
Fridman
W H
WH
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
D017252:CD3 Complex; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma