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


METHODS
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.


CONCLUSIONS
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.
Dierssen
Jan Willem F
JW
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. JWFDierssen@gmail.com
de Miranda
Noel F C C
NF
Mulder
Arend
A
van Puijenbroek
Marjo
M
Verduyn
Willem
W
Claas
Frans H J
FH
van de Velde
Cornelis J H
CJ
Jan Fleuren
Gert
G
Cornelisse
Cees J
CJ
Corver
Willem E
WE
Morreau
Hans
H
D000368:Aged; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D011003:Ploidies
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I