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

Tab. 5.5 Expression of HLA-G in tumor cell lines of distinct origin
5.9 HLA-G Expression: an Immune Privilege for Malignant Cells? 87
Tumor No. of cell lines analyzed HLA-G expression
Breast carcinoma 4 none
Cervical carcinoma 3 none
Colon carcinoma 6 none
Head and neck carcinoma 4 none
Hepatocarcinoma 4 none
Lung carcinoma 4 none
Melanoma 72 1
Neuroblastoma 7 none
Ovarian carcinoma 2 none
RCC 20 3
B and T cell lymphoma 19 none
Histolytic lymphoma 1 1
Myelomonocytes 9 none
pression also occurs at a high frequency. The HLA-G immunoreactivity is correlated
with loss of MHC class Imolecules and IL-10 production in these cells, thus suggesting
an up-regulation of HLA-G by IL-10 [138].
In contrast, other authors show that HLA-G expression in tumors is extremely restricted
[27, 139, 140]. HLA-G is not expressed on the cell surface of more than 70 %
cultured melanoma cell lines and in about 25% primary and metastatic lesions
using polyclonal and monoclonal antibodies in a variety of assays. In addition, tumor
cell lines of distinct origin, such as neuroblastoma, colon carcinoma, sarcoma, breast
carcinoma and bladder carcinoma, lack HLA-G expression [140]. The conflicting information
in the literature cannot be attributed to the specificity of antibodies used
by various investigators, since at least some reagents were used in all studies [137].
Furthermore, it is unlikely that they reflect differences in the sensitivity of the assays
used by the various investigators, since similar methodologies were utilized. Thus,
differences in the characteristics of the cell lines and lesions analyzed appear to be
most likely the source of conflicting results. It is also noteworthy that neither Garrido's
group [136] nor Ferrone et al. (unpublished results) have detected HLA-G proteins
in melanoma cell lines incubated in vitro with IFN-a, IFN-g or TNF-a, although
IFN-a induced HLA-G mRNA expression in at least one cell line. The lack of HLA-G
translation in spite of the constitutive expression of transcripts of different sizes corresponding
to various HLA-G isoforms has been found in several melanoma cell
lines. These findings do not reflect structural abnormalities of HLA-G genes since
sequencing of HLA-G transcripts from three melanoma cell lines detected no mutations.
In view of the low HLA-G mRNA levels found in most of the melanoma cell
lines analyzed, it is noteworthy that the lack of detection of HLA-G proteins does not
reflect their expression by only a subpopulation of melanoma cells, since immunofluorescence
staining of melanoma cell lines with anti-HLA-G mAb has not detected
any HLA-G + cells in a minor subpopulation. Thus, impaired detection of HLA-G proteins
in melanoma cell lines expressing HLA-G mRNA may be caused by protein le-