title: High-resolution analysis of HLA class I alterations in colorectal cancer.
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.
  
  
  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.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. JWFDierssen@gmail.com
authors.forename: Jan Willem F
authors.initials: JW
authors.lastname: Dierssen
authors.forename: Noel F C C
authors.initials: NF
authors.lastname: de Miranda
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Marjo
authors.initials: M
authors.lastname: van Puijenbroek
authors.forename: Willem
authors.initials: W
authors.lastname: Verduyn
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Gert
authors.initials: G
authors.lastname: Jan Fleuren
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: Willem E
authors.initials: WE
authors.lastname: Corver
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
mesh_terms: 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
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I