Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Baechle, JJ; Hanna, DN; Sekhar, KR; Rathmell, JC; Rathmell, WK; Baregamian, N
Published Date
- November 2021
Published In
Volume / Issue
- 25 / 21
Start / End Page
- 10061 - 10072
PubMed ID
- 34664400
Pubmed Central ID
- PMC8572764
Electronic International Standard Serial Number (EISSN)
- 1582-4934
Digital Object Identifier (DOI)
- 10.1111/jcmm.16936
Language
- eng
Conference Location
- England