Cancer-testis Antigen FATE1 Expression in Adrenocortical Tumors Is Associated with A Pervasive Autoimmune Response and Is A Marker of Malignancy in Adult, but Not Children, ACC

Mabrouka Doghman-Bouguerra; Pascal Finetti; Nelly Durand; Ivy Zortéa S Parise; Silviu Sbiera; Giulia Cantini; Letizia Canu; Ségolène Hescot; Mirna M O Figueiredo; Heloisa Komechen; Iuliu Sbiera; Gabriella Nesi; Angelo Paci; Abir Al Ghuzlan; Daniel Birnbaum; Eric Baudin; Michaela Luconi; Martin Fassnacht; Bonald C Figueiredo; François Bertucci; Enzo Lalli

doi:10.3390/cancers12030689

Cancer-testis Antigen FATE1 Expression in Adrenocortical Tumors Is Associated with A Pervasive Autoimmune Response and Is A Marker of Malignancy in Adult, but Not Children, ACC

Cancers (Basel). 2020 Mar 14;12(3):689. doi: 10.3390/cancers12030689.

Authors

Mabrouka Doghman-Bouguerra^{1

2}, Pascal Finetti³, Nelly Durand^{1

2}, Ivy Zortéa S Parise^{2

4}, Silviu Sbiera^{5

6}, Giulia Cantini⁷, Letizia Canu⁷, Ségolène Hescot⁸, Mirna M O Figueiredo^{2

4}, Heloisa Komechen^{2

4}, Iuliu Sbiera^{5

6}, Gabriella Nesi⁹, Angelo Paci¹⁰, Abir Al Ghuzlan¹⁰, Daniel Birnbaum³, Eric Baudin¹⁰, Michaela Luconi⁷, Martin Fassnacht^{5

6}, Bonald C Figueiredo^{2

4}, François Bertucci³, Enzo Lalli^{2

11}

Affiliations

¹ Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS, 660 route des Lucioles-Sophia Antipolis, 06560 Valbonne, France.
² NEOGENEX-CANCER CNRS International Associated Laboratory, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France; 1532 Av. Silva Jardim, Curitiba PR 80250-200, Brazil.
³ Laboratoire d'Oncologie Prédictive, CRCM, Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR7258, Aix-Marseille Université, 232 Bd. Ste-Marguerite, 13009 Marseille, France.
⁴ Department, Pelé Pequeno Principe Research Institute, 1532 Av. Silva Jardim, Curitiba PR 80250-200, Brazil.
⁵ Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, 2 Josef-Schneider-Straße, 97080 Würzburg, Germany.
⁶ Comprehensive Cancer Center Mainfranken, University of Würzburg, 6 Josef-Schneider-Straße, 97080 Würzburg, Germany.
⁷ Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 6 viale Pieraccini, 50139 Florence, Italy.
⁸ Service de Médecine Nucléaire, Institut Curie, 35 rue Dailly, 92210 Saint Cloud, France.
⁹ Division of Pathological Anatomy, Department of Health Sciences, University of Florence, 6 viale Pieraccini, 50139 Florence, Italy.
¹⁰ Department of Neuro-Endocrine Tumors, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94800 Villejuif, France.
¹¹ Inserm, Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles - Sophia Antipolis, 06560 Valbonne, France.

Abstract

The SF-1 transcription factor target gene FATE1 encodes a cancer-testis antigen that has an important role in regulating apoptosis and response to chemotherapy in adrenocortical carcinoma (ACC) cells. Autoantibodies directed against FATE1 were previously detected in patients with hepatocellular carcinoma. In this study, we investigated the prevalence of circulating anti-FATE1 antibodies in pediatric and adult patients with adrenocortical tumors using three different methods (immunofluorescence, ELISA and Western blot). Our results show that a pervasive anti-FATE1 immune response is present in those patients. Furthermore, FATE1 expression is a robust prognostic indicator in adult patients with ACC and is associated with increased steroidogenic and decreased immune response gene expression. These data can open perspectives for novel strategies in ACC immunotherapy.

Keywords: adrenocortical carcinoma; autoantibodies; cancer-testis antigens; immune response.

Grants and funding

15-CE14-0017-01/Agence Nationale de la Recherche