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Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma
Authors:Jordan J Baechle  David N Hanna  Konjeti R Sekhar  Jeffrey C Rathmell  W Kimryn Rathmell  Naira Baregamian
Institution:1. School of Medicine, Meharry Medical College, Nashville, TN, USA;2. Division of Surgical Oncology & Endocrine Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

Contribution: Formal analysis (supporting), Visualization (supporting), Writing - review & editing (supporting);3. Division of Surgical Oncology & Endocrine Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA;4. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA;5. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

Abstract:Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy. Nearly half of ACC tumours overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials have demonstrated significant immunoresistance among cortisol-secreting ACC (CS-ACC) patients when compared to their non-cortisol-secreting (nonCS-ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and hypersecretion is known; however, the impact of the cortisol hypersecretion on ACC tumour microenvironment (TME), immune expression profiles and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS-ACC and CS-ACC tumours to assess the impact of differentially expressed genes (DEGs) by utilizing The Cancer Genome Atlas (TCGA) database. Immunogenomic comparison (CS- vs. nonCS-ACC tumour TMEs) demonstrated an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary prognostic indicators and potential targets within ACC tumour immune landscape. Differentially expressed immune genes with prognostic significance provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS-ACC.
Keywords:adrenocortical carcinoma  cortisol secreting adrenocortical carcinoma  cushing's syndrome  immunometabolism  tumour immunology  tumour microenvironment
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