RESEARCH ARTICLE


Tissue Prognostic Factors in Melanoma: Expression of B7 Family Members B7-H3 and B7-H4 and Death Receptors TRAIL-R1 and TRAILR2



Hélène Aubert-Wastiaux1, 2, Anne-Chantal Knol2, Amir Khammari1, 2, Mélanie Saint-Jean1, 2, Jean-Michel Nguyen3, Gaélle Quereux1, 2, Brigitte Dreno*, 1, 2
1 Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503 CHU Hôtel-Dieu, 1 place Alexis Ricordeau 44093Nantes cedex 1, France
2 Inserm Unit U892, 9 quai Moncousu 44093 Nantes cedex 1 France
3 SEB, CHU Nantes Hopital Saint-Jacques, 85 rue Saint-Jacques 44093 Nantes cedex 1, France


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© 2011 Aubert-Wastiaux et al;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Skin Oncology Department, CIC Biotherapy INSERM 0503, CHU Hotel Dieu, 1 place Alexis Ricordeau, 44035 Nantes cedex 1, France; Tel: 0033240083118; Fax: 0033210083117; E-mail: Brigitte.dreno@wanadoo.fr


Abstract

High resistance rate of melanoma to chemotherapy results in the development of other therapeutic strategies such as immunotherapy. Discrepancies observed in clinical responses to immunotherapy suggest the presence of immune polymorphisms and tumor escape mechanisms.

The objective of this study was to investigate the expression of B7-H3 and B7-H4 which are major stakeholders in immune regulation, and of the death receptors TRAIL-R1 and TRAIL-R2 which play an important role in controlling tumor cell proliferation and apoptosis. The correlation between the expression levels of these proteins and the clinical outcome has also been assessed.

The expression level of the proteins was analyzed on 32 invaded LN samples and on 11 matching tumor cell lines. Immunohistochemical staining and double fluorescent immunostaining on lymph node (LN) frozen sections were performed, as well as flow cytometry on tumor cell lines.

The 4 proteins were expressed in all LN biopsies within a range from 40.6% for TRAIL-R1 to 87.5% for TRAIL-R2. These 4 proteins were rarely expressed by the tumor cell lines except for TRAIL-R2 which was detected in 10 of the 11 cell lines. The expression of these proteins by tumor cell lines is not correlated with in vivo expression found in immunohistochemistry (IHC). It raises the question of the role of the tissue environment in the expression of the proteins. The expression levels of B7-H4, TRAIL-R1, and TRAIL-R2 using IHC were correlated with overall survival. In vivo, high expression levels of B7-H4, TRAIL-R1 or TRAIL-R2 appear as poor prognostic factors.

Keywords: Melanoma, Immunotherapy, B7, TRAIL-R1, TRAIL-R2, Prognostic marker, Lymph node metastasis.