High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis.
BACKGROUND
Human Leukocyte Antigen (HLA)-E is a non-classical class I HLA molecule that can be stabilized by ligands donated by other classical (HLA-A, -B, -C) and non-classical (HLA-G) family members. HLA-E engages a variety of immune receptors expressed by cytotoxic T lymphocytes (CTLs), Natural killer (NK) cells and NK-CTLs. In view of the opposing outcomes (activation or inhibition) of the different HLA-E receptors, the preferred role (if any) of HLA-E expressed in vivo on tumor cells remains to be established.


METHODS
Taking advantage of MEM-E/02, a recently characterized antibody to denatured HLA-E molecules, HLA-E expression was assessed by immunohistochemistry on an archival collection (formalin-fixed paraffin-embedded) of 149 colorectal primary carcinoma lesions paired with their morphologically normal mucosae. Lymphoid infiltrates were assessed for the expression of the HLA-E-specific, inhibitory, non-rearranging receptor NKG2A.


RESULTS
High HLA-E expression did not significantly correlate with the expression of classical HLA-B and HLA-C molecules, but it did correlate with high expression of its preferential ligand donor HLA-A. In addition, it correlated with lymphoid cell infiltrates expressing the inhibitory NKG2A receptor, and was an independent predictor of good prognosis, particularly in a subset of patients whose tumors express HLA-A levels resembling those of their paired normal counterparts (HLA-A). Thus, combination phenotypes (HLA-Elo-int/HLA-AE and HLA-Ehi/HLA-AE) of classical and non-classical class I HLA molecules mark two graded levels of good prognosis.


CONCLUSIONS
These results suggest that HLA-E favors activating immune responses to colorectal carcinoma. They also provide evidence in humans that tumor cells entertain extensive negotiation with the immune system until a compromise between recognition and escape is reached. It is implied that this process occurs stepwise, as predicted by the widely accepted 'immunoediting' model.
Department of Pathology, Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144 Rome, Italy.
Maria
M
Benevolo
Marcella
M
Mottolese
Elisa
E
Tremante
Francesca
F
Rollo
Maria Grazia
MG
Diodoro
Cristiana
C
Ercolani
Isabella
I
Sperduti
Elisa
E
Lo Monaco
Maurizio
M
Cosimelli
Patrizio
P
Giacomini
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000906:Antibodies / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D015999:Multivariate Analysis; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D016707:Tissue Fixation; D000097625:HLA-E Antigens
D000906:Antibodies; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D000097625:HLA-E Antigens