Human leukocyte antigen-E protein is overexpressed in primary human colorectal cancer.
HLA-E is a non-classical MHC molecule whose expression by tumour cells has been recently reported in several human cancer types. We studied HLA-E expression in colorectal cancer patients, its clinical significance and prognostic value, as well as characterized its expression in colorectal cancer cell lines. We analysed HLA-E expression at the transcript level by qRT-PCR in micro-dissected samples and at the protein level by semiquantitative immunohistochemistry on paraffin-embedded tissue sections from 42 biopsies of colorectal cancer patients. We observed that HLA-E transcript and protein are spontaneously overexpressed in a significant proportion of colorectal tumour biopsies, as compared to normal mucosae. We also found a negative correlation between HLA-E expression and the CD57+ cells infiltrate. Moreover, we analysed HLA-E expression in several colorectal cancer cell lines and demonstrated that IFN-gamma upregulates the expression of membrane HLA-E in vitro. Interestingly, we demonstrated that colorectal cancer cell lines overexpressing HLA-E at the cell surface inhibited NK-mediated cell lysis. Although IFN-gamma regulatory role needs further investigation, we provide evidence suggesting that this cytokine, within the tumour microenvironment, could promote HLA-E translocation to the surface of tumour epithelial cells. Furthermore, we showed that upregulation of HLA-E could be a marker of shorter disease-free survival in Dukes' C patients and we suggest that this molecule renders tumours less susceptible to immune attack.
Levy
Estrella Mariel
EM
Centro de Investigaciones Oncológicas (CIO-FUCA), Buenos Aires, Argentina.
Bianchini
Michele
M
Von Euw
Erika María
EM
Barrio
Maria Marcela
MM
Bravo
Alicia Inés
AI
Furman
David
D
Domenichini
Enzo
E
Macagno
Carlos
C
Pinsky
Victor
V
Zucchini
Cinzia
C
Valvassori
Luisa
L
Mordoh
José
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018938:Caco-2 Cells; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018929:Cell Culture Techniques; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006680:HLA Antigens / Q000378:metabolism*; D019073:HT29 Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D021381:Protein Transport; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000494:pharmacology; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D000097625:HLA-E Antigens