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High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis.
Benevolo, Maria; Mottolese, Marcella; Tremante, Elisa; Rollo, Francesca; Diodoro, Maria Grazia; Ercolani, Cristiana; Sperduti, Isabella; Lo Monaco, Elisa; Cosimelli, Maurizio; Giacomini, Patrizio.
Afiliación
  • Benevolo M; Department of Pathology, Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144 Rome, Italy.
J Transl Med ; 9: 184, 2011 Oct 27.
Article en En | MEDLINE | ID: mdl-22032294
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.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Antígenos de Histocompatibilidad Clase I Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Transl Med Año: 2011 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Antígenos de Histocompatibilidad Clase I Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Transl Med Año: 2011 Tipo del documento: Article País de afiliación: Italia