دورية أكاديمية
Characterization of the expression and immunological impact of the transcriptional activator CREB in renal cell carcinoma
| العنوان: | Characterization of the expression and immunological impact of the transcriptional activator CREB in renal cell carcinoma |
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| المؤلفون: | Friedrich, Michael, Stoehr, Christine, Jasinski-Bergner, Simon, Hartmann, Arndt, Wach, Sven, Wullich, Bernd, Steven, André, Seliger, Barbara |
| المصدر: | http://lobid.org/resources/99370673349406441Test#!, 18(1):371. |
| سنة النشر: | 2020 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Promoter Regions, Genetic/genetics [MeSH], Immune cell infiltration, Cyclic AMP Response Element-Binding Protein [MeSH], HLA-G, Renal cell carcinoma, Kidney Neoplasms/genetics [MeSH], HLA-G Antigens/genetics [MeSH], Research, Humans [MeSH], Cancer microenvironment, CREB, Carcinoma, Renal Cell/genetics [MeSH] |
| الوصف: | Background!#!The non-classical human leukocyte antigen (HLA)-G is a strong immunomodulatory molecule. Under physiological conditions, HLA-G induces immunological tolerance in immune privileged tissues, while under pathophysiological situations it contributes to immune escape mechanisms. Therefore, HLA-G could act as a potential immune checkpoint for future anti-cancer immunotherapies. Recent data suggest an aberrant expression of the cAMP response element binding protein (CREB) in clear cell renal cell carcinoma (ccRCC), which is correlated with tumor grade and stage. Furthermore, preliminary reports demonstrated a connection of CREB as a control variable of HLA-G transcription due to CREB binding sites in the HLA-G promoter region. This study investigates the interaction between CREB and HLA-G in different renal cell carcinoma (RCC) subtypes and its correlation to clinical parameters.!##!Methods!#!The direct interaction of CREB with the HLA-G promoter was investigated by chromatin immunoprecipitation in RCC cell systems. Furthermore, the expression of CREB and HLA-G was determined by immunohistochemistry using a tissue microarray (TMA) consisting of 453 RCC samples of distinct subtypes. Staining results were assessed for correlations to clinical parameters as well as to the composition of the immune cell infiltrate.!##!Results!#!There exists a distinct expression pattern of HLA-G and CREB in the three main RCC subtypes. HLA-G and CREB expression were the lowest in chromophobe RCC lesions. However, the clinical relevance of CREB and HLA-G expression differed. Unlike HLA-G, high levels of CREB expression were positively associated to the overall survival of RCC patients. A slightly, but significantly elevated number of tumor infiltrating regulatory T cells was observed in tumors of high CREB expression. Whether this small increase is of clinical relevance has to be further investigated.!##!Conclusions!#!An interaction of CREB with the HLA-G promoter could be validated in RCC cell lines. Thus, for the first time ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6464815Test; https://doi.org/10.1186/s12967-020-02544-0Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526213Test/ |
| DOI: | 10.1186/s12967-020-02544-0 |
| الإتاحة: | https://doi.org/10.1186/s12967-020-02544-0Test https://repository.publisso.de/resource/frl:6464815Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526213Test/ |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.DC811360 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12967-020-02544-0 |
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