Published in:
Open Access
01-12-2006 | Research article
High-resolution analysis of HLA class I alterations in colorectal cancer
Authors:
Jan Willem F Dierssen, Noel FCC de Miranda, Arend Mulder, Marjo van Puijenbroek, Willem Verduyn, Frans HJ Claas, Cornelis JH van de Velde, Gert Jan Fleuren, Cees J Cornelisse, Willem E Corver, Hans Morreau
Published in:
BMC Cancer
|
Issue 1/2006
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Abstract
Background
Previous studies indicate that alterations in Human Leukocyte Antigen (HLA) class I expression are frequent in colorectal tumors. This would suggest serious limitations for immunotherapy-based strategies involving T-cell recognition. Distinct patterns of HLA surface expression might conceal different immune escape mechanisms employed by the tumors and are worth further study.
Method
We applied four-color multiparameter flow cytometry (FCM), using a large panel of alloantigen-specific anti-HLA-A and -B monoclonal antibodies, to study membranous expression of individual HLA alleles in freshly isolated colorectal cancer cell suspensions from 21 patients.
Results
Alterations in HLA class I phenotype were observed in 8 (38%) of the 21 tumors and comprised loss of a single A or B alleles in 4 cases, and loss of all four A and B alleles in the other 4 cases. Seven of these 8 tumors were located on the right side of the colon, and those showing loss of both HLA-A and -B membranous expression were all of the MSI-H phenotype.
Conclusion
FCM allows the discrimination of complex phenotypes related to the expression of HLA class I. The different patterns of HLA class I expression might underlie different tumor behavior and influence the success rate of immunotherapy.