Christoforos Vaxevanis

Martin Luther University Halle-Wittenberg

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Barbara Seliger

Martin Luther University Halle-Wittenberg

Michael Friedrich

Martin Luther University Halle-Wittenberg

Claudia Wickenhauser

University of Cologne

Marcus Bauer

Martin Luther University Halle-Wittenberg

Chiara Massa

Children's Hospital of Philadelphia

Sotirios P. Fortis

St Savas Hospital

Constantin N. Baxevanis

St Savas Hospital

Haifa Kathrin Al‐Ali

University Hospital in Halle

Nectaria N. Sotiriadou

St Savas Hospital

Karthikeyan Subbarayan

Martin Luther University Halle-Wittenberg

Cooperative Institutions

Martin Luther University Halle-Wittenberg

St Savas Hospital

Data Harbor (United States)

University Hospital in Halle

Luther University

National and Kapodistrian University of Athens

Institute of Immunology

San Antonio Military Medical Center

The University of Texas MD Anderson Cancer Center

Uniformed Services University of the Health Sciences

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Erratum to: Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer

Journal for ImmunoTherapy of Cancer (2017)

Sotirios P. Fortis Michael Sofopoulos Nectaria N. Sotiriadou Christoforos Haritos Christoforos Vaxevanis

[This corrects the article DOI: 10.1186/s40425-017-0240-7.].

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10.1186/s40425-017-0248-z

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Citations (3)

Unconventional microRNA role: Enhancing the human leukocyte antigen class I antigen processing pathway via interacting with a silencer

Clinical and Translational Medicine (2024)

Yuan Wang Maria‐Filothei Lazaridou Theresa Kordaß Chiara Massa Christoforos Vaxevanis

10.1002/ctm2.70010

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Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34+ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia

Cancers (2021)

Marcus Bauer Christoforos Vaxevanis Haifa Kathrin Al‐Ali Nadja Jaekel Christin Le Hoa Naumann

Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34+ hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34+ blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8+ and FOXP3+ T cells and only single MUM1p+ B/plasma cells were detected in an area of ≤10 μm to CD34+ HSPC. Conclusions: CD8+ and FOXP3+ T cells are regularly seen in the 10 μm area around CD34+ blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34+ HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.

Bone marrow failure

10.3390/cancers13020186

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Identification of immunomodulatory RNA-binding proteins in tumors

Methods in enzymology on CD-ROM/Methods in enzymology (2019)

Michael Friedrich Maria‐Filothei Lazaridou Jette Rahn Christoforos Vaxevanis Nadine Heimer

10.1016/bs.mie.2019.05.042

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Citations (1)

Targeting the coding sequence: opposing roles in regulating classical and non-classical MHC class I molecules by miR-16 and miR-744

Journal for ImmunoTherapy of Cancer (2020)

Michael Friedrich Christoforos Vaxevanis Katharina Biehl Anja Müeller Barbara Seliger

Background To control gene expression, microRNAs (miRNAs) are of key importance and their deregulation is associated with the development and progression of various cancer types. In this context, a discordant messenger RNA/protein expression pointing to extensive post-transcriptional regulation of major histocompatibility complex (MHC) class I molecules was already shown. However, only a very limited number of miRNAs targeting these molecules have yet been identified. Despite an increasing evidence of coding sequence (CDS)-located miRNA binding sites, there exists so far, no detailed study of the interaction of miRNAs with the CDS of MHC class I molecules. Methods Using an MS2-tethering approach in combination with small RNA sequencing, a number of putative miRNAs binding to the CDS of human leukocyte antigen (HLA)-G were identified. These candidate miRNAs were extensively screened for their effects in the HLA-G-positive JEG3 cell line. Due to the high sequence similarity between HLA-G and classical MHC class I molecules, the impact of HLA-G candidate miRNAs on HLA class I surface expression was also analyzed. The Cancer Genome Atlas data were used to correlate candidate miRNAs and HLA class I gene expression. Results Transfection of candidate miRNAs revealed that miR-744 significantly downregulates HLA-G protein levels. In contrast, overexpression of the candidate miRNAs miR-15, miR-16, and miR-424 sharing the same seed sequence resulted in an unexpected upregulation of HLA-G. Comparable results were obtained for classical MHC class I members after transfection of miRNA mimics into HEK293T cells. Analyses of The Cancer Genome Atlas data sets for miRNA and MHC class I expression further validated the results. Conclusions Our data expand the knowledge about MHC class I regulation and showed for the first time an miRNA-dependent control of MHC class I antigens mediated by the CDS. CDS-located miRNA binding sites could improve the general use of miRNA-based therapeutic approaches as these sites are highly independent of structural variations (e.g. mutations) in the gene body. Surprisingly, miR-16 family members promoted MHC class I expression potentially in a gene activation-like mechanism.

10.1136/jitc-2019-000396

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Citations (29)

An altered miTRAP method for miRNA affinity purification with its pros and cons

Methods in enzymology on CD-ROM/Methods in enzymology (2019)

Simon Jasinski‐Bergner Christoforos Vaxevanis Nadine Heimer Maria‐Filothei Lazaridou Michael Friedrich

cons

10.1016/bs.mie.2019.05.016

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Citations (3)

Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy

Journal for ImmunoTherapy of Cancer (2024)

Christoforos Vaxevanis Michael Bachmann Barbara Seliger

The importance of the immune system in regulating tumor growth by inducing immune cell-mediated cytotoxicity associated with patients' outcomes has been highlighted in the past years by an increasing life expectancy in patients with cancer on treatment with different immunotherapeutics. However, tumors often escape immune surveillance, which is accomplished by different mechanisms. Recent studies demonstrated an essential role of small non-coding RNAs, such as microRNAs (miRNAs), in the post-transcriptional control of immune modulatory molecules. Multiple methods have been used to identify miRNAs targeting genes involved in escaping immune recognition including miRNAs targeting CTLA-4, PD-L1, HLA-G, components of the major histocompatibility class I antigen processing machinery (APM) as well as other immune response-relevant genes in tumors. Due to their function, these immune modulatory miRNAs can be used as (1) diagnostic and prognostic biomarkers allowing to discriminate between tumor stages and to predict the patients' outcome as well as response and resistance to (immuno) therapies and as (2) therapeutic targets for the treatment of tumor patients. This review summarizes the role of miRNAs in tumor-mediated immune escape, discuss their potential as diagnostic, prognostic and predictive tools as well as their use as therapeutics including alternative application methods, such as chimeric antigen receptor T cells.

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Relevance

10.1136/jitc-2024-009774

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Citations (2)

The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer

Cancer Immunology Immunotherapy (2019)

Michael Sofopoulos Sotirios P. Fortis Christoforos Vaxevanis Nectaria N. Sotiriadou Niki Arnogiannaki

CD163

10.1007/s00262-019-02407-8

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Citations (117)

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

International Journal of Molecular Sciences (2020)

Marcus Bauer Christoforos Vaxevanis Nadine Heimer Haifa Kathrin Al‐Ali Nadja Jaekel

Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

10.3390/ijms21197140

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Multiplex immunohistochemistry as a novel tool for the topographic assessment of the bone marrow stem cell niche

Methods in enzymology on CD-ROM/Methods in enzymology (2019)

Marcus Bauer Christoforos Vaxevanis Daniel Bethmann Chiara Massa Nikolaos Pazaitis

Multiplex

Autofluorescence

10.1016/bs.mie.2019.05.055

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Citations (10)