Project B16
Steroid hormones and cancer immunity – learning from adrenocortical carcinoma
Project B16 deals with adrenocortical cancer (ACC), one of the most aggressive endocrine malignancies. It has already been identified that there are two subtypes: the “steroid hormone” and “immune” phenotypes. Connecting to this, we aim to characterize the molecular phenotypes and identify tumour- specific mutant antigens. We hypothesize that the steroid phenotype is associated with glucocorticoid- induced T-cell anergy, so we want to explore the effect of immune- checkpoint inhibitors, as a potential new therapeutic option.
Clinical trials have shown that only a small subset of ACC patients benefits from checkpoint inhibitor (CPI) treatment. An improved understanding of the specific resistance mechanisms in ACC is required, which will then allow the development of improved immunotherapies. We are convinced that the intratumoural glucocorticoid excess plays a major role in T cell depletion and may be therapeutically targeted. It is likely that other factors contribute to the immunologically “cold” tumoural microenvironment that confers resistance to current CPI therapy.
Aims
(I) Elucidate ACC-specific resistance mechanisms and biomarkers of response to immunotherapy
(II) Determine the effects of combined immune checkpoint inhibition and anti-glucocorticoid treatment in vitro and in vivo
(III) Identify novel treatment strategies for an improved immunotherapy against ACC
| Principal Investigators | Institution |
| Prof. Dr. med. Martin Fassnacht | JMU |
| Prof. Dr. med. Dr. rer. nat. Matthias Kroiss | JMU |
