High frequency of HLA-B44 allelic losses in human solid tumors.
Human leukocyte antigen (HLA) class I downregulation, a frequent phenomenon observed in a variety of human tumors, favors tumor immune escape from T-lymphocyte recognition. However, it is not known whether a particular HLA class I allele is lost more frequently than others. To address this question we analyzed HLA class I expression in tumor tissues derived from 300 patients diagnosed as having breast, colorectal, or laryngeal carcinomas. Cryostatic tumor sections and a broad panel of anti-HLA class I monoclonal antibodies were used. We found that the HLA-B44 allele was lost more frequently than other HLA class I alleles, and that the difference was not related with changes in HLA-B44 allele frequencies between patients and controls. In addition, we observed that 35% of the HLA-B44 negative tumors presented HLA haplotype loss associated with loss of heterozygosity. These tests were performed on DNA samples obtained from microdissected tumor tissues. The results seem to indicate that HLA class I allelic losses are not randomly distributed during tumor development but that some HLA class I alleles, and HLA-B44 in particular, are more frequently downregulated and may play an important role in immune escape mechanisms.
Cabrera
Teresa
T
Departamento de Anáslisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Maleno
Isabel
I
Lopez-Nevot
Miguel Angel
MA
Redondo
Maximino
M
Fernandez
Maria Angustias
MA
Collado
Antonia
A
Garrido
Federico
F
D000483:Alleles; D002277:Carcinoma / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009369:Neoplasms / Q000235:genetics*
D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I