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Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

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86<br />

5 Major Histocompatibility Complex Modulation <strong>and</strong> Loss<br />

5.9.1<br />

HLA-G Expression in Tumor Cells of Distinct Origin<br />

Until now, there is limiting information available about HLA-G expression in human<br />

tumors. HLA-G expression has been investigated both at the mRNA <strong>and</strong> protein levels<br />

in a variety of tumor cell lines <strong>and</strong> surgically removed malignant lesions, especially<br />

in melanoma [43]. Both antisera <strong>and</strong> mAb have been utilized in immunohistochemical<br />

binding <strong>and</strong> immunochemical assays. Figure 5.20 shows a representative<br />

example of a flow cytometric staining of untreated <strong>and</strong> IFN-g-treated RCC cells, but<br />

not of autologous renal epithelial cells utilizing the anti-HLA-G mAb MEM [30].<br />

Results in the literature about the frequency of HLA-G expression <strong>by</strong> malignant cells<br />

are conflicting [132±137] (Tab. 5.5). High levels of HLA-G transcripts <strong>and</strong>/or proteins<br />

are found in tumor biopsies <strong>and</strong> cell lines derived from melanoma when compared<br />

to healthy skin or lymph nodes of the same patient [133]. In lung cancer, HLA-G ex-<br />

Fig. 5.20 Differential HLA-G expression <strong>by</strong> RCC<br />

cells <strong>and</strong> <strong>by</strong> normal renal epithelial cells. The untreated<br />

<strong>and</strong> IFN-g-treated RCC cell lines<br />

LE8915RC <strong>and</strong> MZ2733RCC as well as the cell<br />

line MZ2733NN derived from a normal renal<br />

epithelium were subjected to flow cytometric<br />

analysis using the anti-HLA-G-specific mAb<br />

MEM-G9 <strong>and</strong> a murine isotypic control antibody.<br />

The choriocarcinoma cell line JEG-3 served as a<br />

positive control. Results are expressed as histograms<br />

demonstrating constitutive <strong>and</strong> IFN-gmediated<br />

HLA-G expression in the cell lines<br />

JEG3, LE89.15RCC <strong>and</strong> MZ2733RCC, but not in<br />

the normal kidney cell line MZ2733NN.

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