High-resolution analysis of HLA class I alterations in colorectal cancer.

Autor: Dierssen JW; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. JWFDierssen@gmail.com, de Miranda NF, Mulder A, van Puijenbroek M, Verduyn W, Claas FH, van de Velde CJ, Jan Fleuren G, Cornelisse CJ, Corver WE, Morreau H
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2006 Oct 02; Vol. 6, pp. 233. Date of Electronic Publication: 2006 Oct 02.
DOI: 10.1186/1471-2407-6-233
Abstrakt: 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.
Databáze: MEDLINE