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CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival

Overview of attention for article published in Acta Neuropathologica Communications, March 2018
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Title
CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival
Published in
Acta Neuropathologica Communications, March 2018
DOI 10.1186/s40478-018-0521-5
Pubmed ID
Authors

P. S. Zeiner, J. Zinke, D. J. Kowalewski, S. Bernatz, J. Tichy, M. W. Ronellenfitsch, F. Thorsen, A. Berger, M. T. Forster, A. Muller, J. P. Steinbach, R. Beschorner, J. Wischhusen, H. M. Kvasnicka, K. H. Plate, S. Stefanović, B. Weide, M. Mittelbronn, P. N. Harter

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. CD74highand TILhightumors 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.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 49 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 18%
Student > Doctoral Student 8 16%
Researcher 7 14%
Student > Bachelor 5 10%
Professor > Associate Professor 3 6%
Other 7 14%
Unknown 10 20%
Readers by discipline Count As %
Medicine and Dentistry 15 31%
Biochemistry, Genetics and Molecular Biology 6 12%
Agricultural and Biological Sciences 5 10%
Neuroscience 3 6%
Immunology and Microbiology 2 4%
Other 4 8%
Unknown 14 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 September 2018.
All research outputs
#17,932,482
of 23,025,074 outputs
Outputs from Acta Neuropathologica Communications
#1,212
of 1,394 outputs
Outputs of similar age
#240,859
of 331,156 outputs
Outputs of similar age from Acta Neuropathologica Communications
#22
of 23 outputs
Altmetric has tracked 23,025,074 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,394 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,156 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 4th percentile – i.e., 4% of its contemporaries scored the same or lower than it.