TY  - JOUR
A1  - López, Cristina
A1  - Kleinheinz, Kortine
A1  - Aukema, Sietse M.
A1  - Rohde, Marius
A1  - Bernhart, Stephan H.
A1  - Hübschmann, Daniel
A1  - Wagener, Rabea
A1  - Toprak, Umut H.
A1  - Raimondi, Francesco
A1  - Kreuz, Markus
A1  - Waszak, Sebastian M.
A1  - Huang, Zhiqin
A1  - Sieverling, Lina
A1  - Paramasivam, Nagarajan
A1  - Seufert, Julian
A1  - Sungalee, Stephanie
A1  - Russell, Robert B.
A1  - Bausinger, Julia
A1  - Kretzmer, Helene
A1  - Ammerpohl, Ole
A1  - Bergmann, Anke K.
A1  - Binder, Hans
A1  - Borkhardt, Arndt
A1  - Brors, Benedikt
A1  - Claviez, Alexander
A1  - Doose, Gero
A1  - Feuerbach, Lars
A1  - Haake, Andrea
A1  - Hansmann, Martin-Leo
A1  - Hoell, Jessica
A1  - Hummel, Michael
A1  - Korbel, Jan O.
A1  - Lawerenz, Chris
A1  - Lenze, Dido
A1  - Radlwimmer, Bernhard
A1  - Richter, Julia
A1  - Rosenstiel, Philip
A1  - Rosenwald, Andreas
A1  - Schilhabel, Markus B.
A1  - Stein, Harald
A1  - Stilgenbauer, Stephan
A1  - Stadler, Peter F.
A1  - Szczepanowski, Monika
A1  - Weniger, Marc A.
A1  - Zapatka, Marc
A1  - Eils, Roland
A1  - Lichter, Peter
A1  - Loeffler, Markus
A1  - Möller, Peter
A1  - Trümper, Lorenz
A1  - Klapper, Wolfram
A1  - Hoffmann, Steve
A1  - Küppers, Ralf
A1  - Burkhardt, Birgit
A1  - Schlesner, Matthias
A1  - Siebert, Reiner
T1  - Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma
JF  - Nature Communications
N2  - Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
KW  - cancer genomics
KW  - lymphocytes
KW  - lymphoid tissues
KW  - oncology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237281
VL  - 10
ER  - 
TY  - JOUR
A1  - Landwehr, Laura-Sophie
A1  - Altieri, Barbara
A1  - Schreiner, Jochen
A1  - Sbiera, Iuliu
A1  - Weigand, Isabel
A1  - Kroiss, Matthias
A1  - Fassnacht, Martin
A1  - Sbiera, Silviu
T1  - Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma
JF  - Journal for ImmunoTherapy of Cancer
N2  - 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 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.
KW  - immunity
KW  - immunotherapy
KW  - lymphocytes
KW  - tumor-infiltrating
KW  - t-lymphocytes
KW  - tumor microenvironment
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229893
VL  - 8
ER  -