Immunity in Adrenocortical Carcinoma Patients – Interplay Between Anti-Cancer Immunity and Steroid Hormons

Presentation Number: LB MON 49
Date of Presentation: April 3rd, 2017

Silviu Sbiera*1, Thomas Dexneit1, Iuliu Sbiera1, Jochen Schreiner2, Cristina Lucia Ronchi1, Matthias Kroiss1 and Martin Fassnacht1
1University Hospital Wuerzburg, Wuerzburg, Germany, 2University Hospital Wuerzburg

Abstract

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 the changes induced by ACC on circulating immune cells we isolated the PBMCs from blood of 19 healthy controls=HC and 163 ACC patients (41 tumour free=TF, 82 with tumour present but without cortisol excess=TP and 40 with both tumour and cortisol excess=CE) and performed FACS analyses to quantify the T-cells (CD3), B-cells (CD19), monocytes (CD14) and regulatory T-cells (T-reg) as a sign of immune suppression (CD4+ CD25high FOXP3+). We also analysed, using immunofluorescence, the presence of tumour infiltrating T-helper cells (CD3+ CD4+), cytotoxic T-cells (CD3+ CD8+), Tregs, B-cells, dendritic cells (CD209+) in full FFPE from 58 primary ACC tumours. Furthermore, the expression of immune checkpoint-markers programmed death 1 (PD1) and its ligand PDL1 was analysed by IHC. From the peripheral cells only the percentage of Treg in the circulating T-cell population correlated significantly with the 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). Furthermore, using the median as cut-off, the 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.

 

Nothing to Disclose: SS, TD, IS, JS, CLR, MK, MF