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