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-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.
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Authors | Maria Benevolo, Marcella Mottolese, Elisa Tremante, Francesca Rollo, Maria Grazia Diodoro, Cristiana Ercolani, Isabella Sperduti, Elisa Lo Monaco, Maurizio Cosimelli, Patrizio Giacomini |
Journal | Journal of translational medicine
(J Transl Med)
Vol. 9
Pg. 184
(Oct 27 2011)
ISSN: 1479-5876 [Electronic] England |
PMID | 22032294
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- CD8 Antigens
- HLA-E antigen
- Histocompatibility Antigens Class I
- NK Cell Lectin-Like Receptor Subfamily C
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Alleles
- Antibodies
(immunology)
- CD8 Antigens
(immunology)
- Colorectal Neoplasms
(diagnosis, immunology, pathology)
- Female
- Histocompatibility Antigens Class I
(genetics, immunology)
- Humans
- Immunohistochemistry
- Intestinal Mucosa
(immunology, pathology)
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Models, Immunological
- Multivariate Analysis
- NK Cell Lectin-Like Receptor Subfamily C
(immunology)
- Neoplasm Staging
- Paraffin Embedding
- Prognosis
- Tissue Fixation
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