Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma.
An impaired immune response is frequently observed in cancer patients and tumor-bearing mice. T-cells from mice with an experimental colon carcinoma were recently shown to express T-cell receptors that completely lacked the signal-transducing molecule CD3 zeta. Here, we have investigated the expression of the signal-transducing molecule zeta on lymphocytes from 14 patients with colorectal carcinomas using flow cytometric analysis of permeabilized cells with a monoclonal antibody (TIA-2; IgG1) specific for the cytoplasmic domain of the zeta chain as well as with immunoprecipitation and analysis on diagonal gel electrophoresis. We demonstrate that T-cells isolated from the tumors of the patients express significantly less CD3 zeta than T-cells in the peripheral blood of the same patients and that the peripheral blood of the patients express decreased levels of zeta chains, as compared to the levels found in lymphocytes from healthy controls. This decreased expression was also observed on zeta chains associated with the low affinity Fc receptor for IgG found in tumor-infiltrating NK cells (Fc gamma RIIIA alpha; CD16).
Nakagomi
H
H
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Petersson
M
M
Magnusson
I
I
Juhlin
C
C
Matsuda
M
M
Mellstedt
H
H
Taupin
J L
JL
Vivier
E
E
Anderson
P
P
Kiessling
R
R
D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry*; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D015398:Signal Transduction
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain