Endocrine Abstracts

Background: Immune checkpoint therapy response rate in adrenocortical carcinoma (ACC) is only ~15%. Glucocorticoid (GC) secretion is present in ~60% of tumours, associated with adverse outcome and has been associated with an immunologically cold tumoural microenvironment. On the other hand, activation of the Wnt/ß-Catenin pathway has been suggested to contribute to reduced immune infiltration.Aims: First, we aim to improve the understanding of cellu...

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy that produces glucocorticoids in 60% of cases causing clinically relevant hypercortisolism. Since, we observed in another study, that shaping these immunosuppressive and life-threatining properties with corticosteroid inhibitors not only led to a glucocorticoid receptor-related downregulation of ROR1 but also to the upregulation of another promising membrane bound oncogenic antigen* (AG), we sought to...

BackgroundAdrenocortical carcinoma (ACC) is a rare but devastating tumour of the adrenal gland and the molecular mechanisms of pathogenesis remain incompletely understood. To gain novel insights into the cellular landscape of ACC, we compared single nuclei RNA sequencing (snRNA-seq) datasets from ACC and normal adrenal glands (NAGs).Methods: We isolated single nuclei from 12 ACC snap-frozen samples, including 6 primary tumours, 3 local r...

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine disease in which 60% of patients show endogenous glucocorticoid (GC) secretion that potentially contributes to a lack of immune cell infiltration and limited efficacy of immunotherapeutic approaches. In another study, we already demonstrated potent antitumor efficacy or ROR1 CAR-T cells in preclinical models of ACC. Nevertheless, solid tumors often show cell intrinsic resistance mechanisms to CAR-T c...

Background: Adrenocortical carcinoma (ACC) is a very rare and aggressive, endocrine malignancy with still limited treatment options. Approximately 60% of patients with ACC show endogenous glucocorticoid excess which could be one potential cause, why first clinical trials with immunotherapies, like immune checkpoint inhibitors, showed only modest results. Due to the lack of an ACC-specific antigen structure, other immunotherapeutic approaches, like specialized cancer treatments...

# These authors contributed equallyIntroduction: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with poor prognosis and limited treatment options. In addition, ACC is characterized by endogenous glucocorticoid (GC) excess in 60% of cases which is hypothesized to be one reason, why first clinical trials evaluating the potency of immune checkpoint blockade showed only modest results. Here, we report the identificati...

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with poor prognosis and very limited treatment options in advanced disease. The only curative approach is complete surgical resection. Additionally, 60% of patients show endogenous glucocorticoid (GC) excess with clinical apparent hypercortisolism and low to no immune cell infiltration. To date, no therapeutically relevant surface markers are known for ACC, which is why it has not been con...

Background: Adrenocortical cancer (ACC) is a rare malignant neoplasm with a dismal prognosis, particularly in advanced disease. For these patients only limited therapeutic options are available. Adavosertib (AZD1775) is a potent inhibitor of tyrosine kinase WEE1 that regulates cell cycle checkpoints, slowing cell cycle progression and leading to mitotic entry in the presence of DNA damage. Therefore, its use could potentiate existing DNA damage-based therapies. Here, we evalua...