TY  - JOUR
A1  - Zeiner, P. S.
A1  - Zinke, J.
A1  - Kowalewski, D. J.
A1  - Bernatz, S.
A1  - Tichy, J.
A1  - Ronellenfitsch, M. W.
A1  - Thorsen, F.
A1  - Berger, A.
A1  - Forster, M. T.
A1  - Muller, A.
A1  - Steinbach, J. P.
A1  - Beschorner, R.
A1  - Wischhusen, J.
A1  - Kvasnicka, H. M.
A1  - Plate, K. H.
A1  - Stefanović, S.
A1  - Weide, B.
A1  - Mittelbronn, M.
A1  - Harter, P. N.
T1  - CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival
JF  - Acta Neuropathologica Communications
N2  - Abstract
Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.

We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line.

We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected.

In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.
KW  - CD74
KW  - HLA class II
KW  - brain metastasis
KW  - HLA peptidome
KW  - tumor infiltrating lymphocytes
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233882
VL  - 6
ER  - 
TY  - JOUR
A1  - Stühler, R.
A1  - Kowalewski, A.
A1  - Reis, F.
A1  - Jungblut, D.
A1  - Dominguez, F.
A1  - Scharf, B.
A1  - Li, G.
A1  - Schäfer, J.
A1  - Hankiewicz, E. M.
A1  - Claessen, R.
T1  - Effective lifting of the topological protection of quantum spin Hall edge states by edge coupling
JF  - Nature Communications
N2  - The scientific interest in two-dimensional topological insulators (2D TIs) is currently shifting from a more fundamental perspective to the exploration and design of novel functionalities. Key concepts for the use of 2D TIs in spintronics are based on the topological protection and spin-momentum locking of their helical edge states. In this study we present experimental evidence that topological protection can be (partially) lifted by pairwise coupling of 2D TI edges in close proximity. Using direct wave function mapping via scanning tunneling microscopy/spectroscopy (STM/STS) we compare isolated and coupled topological edges in the 2D TI bismuthene. The latter situation is realized by natural lattice line defects and reveals distinct quasi-particle interference (QPI) patterns, identified as electronic Fabry-Pérot resonator modes. In contrast, free edges show no sign of any single-particle backscattering. These results pave the way for novel device concepts based on active control of topological protection through inter-edge hybridization for, e.g., electronic Fabry-Pérot interferometry.
KW  - topological insulators
KW  - two-dimensional materials
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300886
VL  - 13
ER  -