Endocrine Abstracts

Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. By applying a ‘multiple omics’ approach, we recently identified two distinct subgroups of ACC patients, a good prognosis “immune” and bad prognosis “steroid” phenotype.

We hypothesized that the steroid phenotype is associated with glucocorticoid-induced suppression that can be ‘rescued’ by reactivating the immune system using immune checkpoint inhibitors and inhibitors of steroidogenesis.

To assess changes induced by ACC on circulating immune cells we isolated PBMCs from blood of 19 healthy controls=HC and 163 ACC patients (41: tumour free=TF, 82: tumour present without cortisol excess=TP and 40: tumour present and cortisol excess=CE) and performed FACS analyses to quantify T-cells (CD3+CD4+ and CD3+CD8+), B-cells (CD19), monocytes (CD14) and regulatory T-cells (T-reg) as a sign of immune suppression (CD4+CD25^highFOXP3+). Using immunofluorescence, we analysed the presence of tumour infiltrating T-cells, Tregs, B-cells, dendritic cells (CD209+) in full FFPE from 58 primary ACC tumours. Furthermore, expression of immune checkpoint-markers programmed death 1 (PD1) and its ligand PDL1 was analysed by IHC.

From the peripheral cells the percentage of Treg in the circulating T-cell population correlated significantly with tumoural and steroid secretion status (4.4±1.2 in HC, 7.9±6.1 in TF, 9.0±7.9 in TP and 11.0±7.8 in CE, P<0.01). Using median as cut-off, patients with increased percentage of peripheral Treg had a lower survival rate (HR=1.8, 95%CI 1.0-3.1, P=0.02). Most tumours presented a tumour infiltrate (T-cells: 80%, 37±65 cells/HPF, cytotoxic T-cells: 72%, 24.9±53.0, T-helper: 57%, 19.3±16.9 cells/HPF, Treg: 48%, 3.8±3.8, dendritic cells: 73%, 5.8±3.7, B-cells: 0%, PD1: 36%, 14.7±30.1, PDL-1: 83%, 34.6±81.6). The only tumour infiltrating cells associated overall survival were the CD4+T-helper cells (HR for death: 0.34, 95%CI 0.12–0.95, P=0.005).

In conclusion, ACC patients are characterized by increased circulating immune inhibitory Tregs and tumour infiltrating CD4+T-helper cells have a positive influence on patient survival.