Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-229893
- Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in similar to 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. Methods We performed immunofluorescence analysis to visualize tumor-infiltrating T cellsBackground Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in similar to 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. Methods We performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3\(^+\)), T helper cells (CD3\(^+\)CD4\(^+\)), cytotoxic T cells (CD3\(^+\)CD8\(^+\)) and regulatory T cells (Tregs; CD3\(^+\)CD4\(^+\)FoxP3\(^+\)) 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). Results 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\(^+\)- and CD8\(^+\) 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). Conclusion 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.…
Autor(en): | Laura-Sophie Landwehr, Barbara Altieri, Jochen Schreiner, Iuliu Sbiera, Isabel Weigand, Matthias Kroiss, Martin Fassnacht, Silviu Sbiera |
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URN: | urn:nbn:de:bvb:20-opus-229893 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Klinische Biochemie und Pathobiochemie |
Medizinische Fakultät / Medizinische Klinik und Poliklinik I | |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Journal for ImmunoTherapy of Cancer |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 8 |
Aufsatznummer: | e000469 |
Originalveröffentlichung / Quelle: | Journal for ImmunoTherapy of Cancer 2020;8:e000469. doi:10.1136/jitc-2019-000469 |
DOI: | https://doi.org/10.1136/jitc-2019-000469 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | immunity; immunotherapy; lymphocytes; t-lymphocytes; tumor microenvironment; tumor-infiltrating |
Datum der Freischaltung: | 22.04.2021 |
Sammlungen: | Open-Access-Publikationsfonds / Förderzeitraum 2020 |
Lizenz (Deutsch): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |