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

74 5 Major Histocompatibility Complex Modulation and Loss
Fig. 5.13 Representative examples
of defects in HLA class I
antigen expression in surgically
removed carcinoma lesions of
distinct origin. Frozen tissue
sections were stained in the immunoperoxidase
reaction with
respective anti-HLA class I
mAbs. (Top panels) The lack of
staining of the breast carcinoma
lesions in the right top panel by
the anti-HLA-A, -B and -C mAbs
indicates a total HLA class I
antigen loss in this lesion.
(Middle panels) The lack of
staining of the lesion with an
anti-HLA-B mAb indicates a selective
loss of the gene products
of HLA-B loci. (Bottom panels)
The lack of staining of the lesion
with the anti-HLA-A30 mAb indicates
selective loss of the HLA
class I allospecificity. (see color
plates page XXII)
MHC class Iabnormalities might be missed if the different MHC molecules potentially
expressed on the cell surface are not independently measured.
There exist distinct mechanisms resulting in allele- or locus-specific decrease or loss
of MHC class Iantigens. Loss of one MHC class Ihaplotype associated with LOH at
chromosome 6p21 has been described in cell lines derived from melanoma, colon
carcinoma, pancreatic carcinoma and cervical carcinoma lesions [33, 67±71]
(Tab. 5.3). This altered MHC class Iphenotype can be easily and reproducibly detected
by microsatellite marker analysis using PCR amplification. A representative
example is shown in Fig. 5.14 for a colon carcinoma cell line. This phenotype is
caused by loss of variable portions of genomic DNA which is attributable to chromosomal
segregation, non-dysjunction or mitotic recombination in the short arm of
chromosome 6, where the MHC region has been mapped [72]. The frequency of haplotype
loss in tumors derived from different tissues has not yet been evaluated in de-
Tab. 5.3 HLA haplotype loss: LOH at 6p21
Tumor cell line Tumor References
FM55 melanoma 149
FM37 melanoma
IMIM-PC2 pancreatic carcinoma 68
NW145 melanoma 150
OCM-3 uveal melanoma 154
877 cervical carcinoma 157
CC-11 cervical carcinoma 155