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

结直肠癌 HLA I 类变异的高分辨率分析

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作者:Jan Willem F Dierssen, Noel F C C de Miranda, Arend Mulder, Marjo van Puijenbroek, Willem Verduyn, Frans H J Claas, Cornelis J H van de Velde, Gert Jan Fleuren, Cees J Cornelisse, Willem E Corver, Hans Morreau

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.

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.

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.

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