Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma

• DOI: 10.1136/jitc-2019-000469
• Publication Date: 2020-05-30T21:30:25Z
• Authors: Laura-Sophie Land...; Barbara Altieri; Jochen Schreiner; Iuliu Sbiera; Isabel Weigand; Matthias Kroiss; Martin Fassnacht; Silviu Sbiera
• Keywords: Tumor-infiltrating lymphocytes; Mitotane

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess present in ~60% of patients and associated with particularly poor prognosis. Results first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) ACC association glucocorticoids as potential explanation for resistance to immunotherapy.We performed immunofluorescence analysis visualize cells (CD3+), helper (CD3+CD4+), cytotoxic (CD3+CD8+) regulatory (Tregs; CD3+CD4+FoxP3+) 146 tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data cell infiltration correlated (including excess).86.3% showed tumor infiltrating (7.7 cells/high power field (HPF)), including (74.0%, 6.7 cells/HPF), (84.3%, 5.7 cells/HPF) Tregs (49.3%, 0.8 cells/HPF). The number TILs was better overall survival (HR death: 0.47, 95% CI 0.25 0.87), which true CD4+- CD8+ subpopulations well. In localized, non-metastatic ACC, the favorable impact on recurrence-free manifested even independently ENSAT (European Network Study Adrenal Tumors) stage, resection status Ki67 index. negatively (Phi=-0.290, p=0.009). Patients low had (27 vs. 121 months without excess).Glucocorticoid depletion unfavorable To reactivate system by inhibitors, an inhibition adrenal steroidogenesis might be pivotal should tested prospective studies.