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

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.

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

“…Among the determinants of malignant behavior of this tumor, a critical role is played by molecules modulating cell death and resistance to chemotherapeutic agents. One of these molecules is the steroidogenic factor-1 (SF-1) target gene FATE1, encoding for a protein localized at the interface between mitochondria and endoplasmic reticulum, where it regulates Ca 2+ -dependent and mitotane-induced apoptosis in ACC cells by modulating the distance between the two organelles [ 101 ]. FATE1 is expressed at high levels in about 40% of adult ACC and its expression is significantly and inversely correlated with patients’ overall survival.…”

“…High steroid production by FATE1-expressing tumors is likely to create an unfavorable environment for immune cell infiltration and local response against this antigen. On the other hand, FATE1 expression in the most aggressive group of ACC could open new perspectives for immunotherapy using vaccination against this and other cancer neoantigens [ 101 ].…”

Circulating Fascin 1 as a Promising Prognostic Marker in Adrenocortical Cancer

“…A different approach reported in the literature involves the research of circulating autoantibodies against FSCN1 instead of measuring serum FSCN1 levels, even though this alternative strategy might lack sensitivity (21). However, this approach might be of a potential value in ACC, as previously demonstrated for another potential marker of ACC, FATE-1 (22).…”

A Targeted Bioinformatics Assessment of Adrenocortical Carcinoma Reveals Prognostic Implications of GABA System Gene Expression

“…ABAT encodes a dual-function mitochondrial enzyme responsible for both GABA catabolism and maintenance of mitochondrial DNA copy number [ 69 ]. Other genes encoding mitochondrial proteins that are prognostic for survival in ACC include PINK1 , encoding a mitochondrial serine/threonine kinase [ 18 , 70 ], and FATE1 , encoding a mitochondrial fission factor-family protein [ 71 , 72 ]. Although not tested in ACC clinical trials in the United States ( ), drugs targeting TCA cycle-associated enzymes are now in clinical trials for various other cancers [ 73 ].…”