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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number184
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
Publication statusPublished - Oct 27 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Fingerprint Dive into the research topics of 'High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis'. Together they form a unique fingerprint.

  • Cite this