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Open Access 01-12-2011 | Research

High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

Authors: Maria Benevolo, Marcella Mottolese, Elisa Tremante, Francesca Rollo, Maria Grazia Diodoro, Cristiana Ercolani, Isabella Sperduti, Elisa Lo Monaco, Maurizio Cosimelli, Patrizio Giacomini

Published in: Journal of Translational Medicine | Issue 1/2011

Abstract

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-E^lo-int/HLA-AE and HLA-E^hi/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.

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Title: High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis
Authors: Maria Benevolo
Marcella Mottolese
Elisa Tremante
Francesca Rollo
Maria Grazia Diodoro
Cristiana Ercolani
Isabella Sperduti
Elisa Lo Monaco
Maurizio Cosimelli
Patrizio Giacomini
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-9-184

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